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Author Bisgaard, H.; Bonnelykke, K. url  doi
openurl 
  Title Fish Oil in Pregnancy and Asthma in Offspring Type
  Year 2017 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 376 Issue 12 Pages 1191-1192  
  Keywords *Asthma; Dietary Supplements; Family; Fatty Acids, Omega-3; Female; *Fish Oils; Humans; Pregnancy  
  Abstract  
  Address Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen, Denmark  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bonnelykke, K.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28328328 Approved no  
  Call Number Serial 357  
Permanent link to this record
 

 
Author Bisgaard, H.; Stokholm, J.; Chawes, B.L.; Vissing, N.H.; Bjarnadottir, E.; Schoos, A.-M.M.; Wolsk, H.M.; Pedersen, T.M.; Vinding, R.K.; Thorsteinsdottir, S.; Folsgaard, N.V.; Fink, N.R.; Thorsen, J.; Pedersen, A.G.; Waage, J.; Rasmussen, M.A.; Stark, K.D.; Olsen, S.F.; Bonnelykke, K. url  doi
openurl 
  Title Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring Type Journal Article
  Year 2016 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 375 Issue 26 Pages 2530-2539  
  Keywords  
  Abstract Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. Results A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. Conclusions Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).  
  Address From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) – all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.)  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bonnelykke, K.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28029926 Approved no  
  Call Number Serial 334  
Permanent link to this record
 

 
Author Caliskan, M.; Bochkov, Y.A.; Kreiner-Moller, E.; Bonnelykke, K.; Stein, M.M.; Du, G.; Bisgaard, H.; Jackson, D.J.; Gern, J.E.; Lemanske, R.F.J.; Nicolae, D.L.; Ober, C. url  doi
openurl 
  Title Rhinovirus wheezing illness and genetic risk of childhood-onset asthma Type Journal Article
  Year 2013 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 368 Issue 15 Pages 1398-1407  
  Keywords Asthma/*genetics/virology; Child; Chromosomes, Human, Pair 17; Common Cold/*complications; DNA/isolation & purification; Gene Expression; Genetic Predisposition to Disease; Genotype; Humans; Leukocytes, Mononuclear; Polymorphism, Single Nucleotide; RNA/isolation & purification; *Respiratory Sounds/genetics; Respiratory Syncytial Virus Infections/complications; Respiratory Syncytial Viruses; *Rhinovirus; Risk  
  Abstract BACKGROUND: Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts. METHODS: We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs). RESULTS: The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific. CONCLUSIONS: Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.).  
  Address Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. caliskan@uchicago.edu  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Caliskan, M. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Ober, C.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23534543; PMCID:PMC3755952 Approved no  
  Call Number Serial 92  
Permanent link to this record
 

 
Author Sleiman, P.M.A.; Flory, J.; Imielinski, M.; Bradfield, J.P.; Annaiah, K.; Willis-Owen, S.A.G.; Wang, K.; Rafaels, N.M.; Michel, S.; Bonnelykke, K.; Zhang, H.; Kim, C.E.; Frackelton, E.C.; Glessner, J.T.; Hou, C.; Otieno, F.G.; Santa, E.; Thomas, K.; Smith, R.M.; Glaberson, W.R.; Garris, M.; Chiavacci, R.M.; Beaty, T.H.; Ruczinski, I.; Orange, J.S.; Allen, J.; Spergel, J.M.; Grundmeier, R.; Mathias, R.A.; Christie, J.D.; von Mutius, E.; Cookson, W.O.C.; Kabesch, M.; Moffatt, M.F.; Grunstein, M.M.; Barnes, K.C.; Devoto, M.; Magnusson, M.; Li, H.; Grant, S.F.A.; Bisgaard, H.; Hakonarson, H. url  doi
openurl 
  Title Variants of DENND1B associated with asthma in children Type Journal Article
  Year 2010 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 362 Issue 1 Pages 36-44  
  Keywords African Continental Ancestry Group/genetics; Asthma/*genetics; Case-Control Studies; Child; *Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 17; Death Domain Receptor Signaling Adaptor Proteins/*genetics; European Continental Ancestry Group/*genetics; Female; *Genetic Predisposition to Disease; *Genome-Wide Association Study; Guanine Nucleotide Exchange Factors/*genetics; Humans; Male; Meta-Analysis as Topic; North America; Odds Ratio; *Polymorphism, Single Nucleotide; Receptors, Tumor Necrosis Factor/metabolism  
  Abstract BACKGROUND: Asthma is a complex disease that has genetic and environmental causes. The genetic factors associated with susceptibility to asthma remain largely unknown. METHODS: We carried out a genomewide association study involving children with asthma. The sample included 793 North American children of European ancestry with persistent asthma who required daily inhaled glucocorticoid therapy and 1988 matched controls (the discovery set). We also tested for genomewide association in an independent cohort of 917 persons of European ancestry who had asthma and 1546 matched controls (the replication set). Finally, we tested for an association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31 and asthma in 1667 North American children of African ancestry who had asthma and 2045 ancestrally matched controls. RESULTS: In our meta-analysis of all samples from persons of European ancestry, we observed an association, with genomewide significance, between asthma and SNPs at the previously reported locus on 17q21 and an additional eight SNPs at a novel locus on 1q31. The SNP most strongly associated with asthma was rs2786098 (P=8.55x10(-9)). We observed replication of the association of asthma with SNP rs2786098 in the independent series of persons of European ancestry (combined P=9.3x10(-11)). The alternative allele of each of the eight SNPs on chromosome 1q31 was strongly associated with asthma in the children of African ancestry (P=1.6x10(-13) for the comparison across all samples). The 1q31 locus contains the 1q31 locus contains DENND1B, a gene expressed by natural killer cells and dendritic cells. DENND1B protein is predicted to interact with the tumor necrosis factor alpha receptor [corrected]. CONCLUSIONS: We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma.  
  Address Center for Applied Genomics, Philadelphia, PA 19104-4318, USA  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Sleiman, P.M.A. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Hakonarson, H.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20032318 Approved no  
  Call Number Serial 142  
Permanent link to this record
 

 
Author Bisgaard, H.; Hermansen, M.N.; Buchvald, F.; Loland, L.; Halkjaer, L.B.; Bonnelykke, K.; Brasholt, M.; Heltberg, A.; Vissing, N.H.; Thorsen, S.V.; Stage, M.; Pipper, C.B. url  doi
openurl 
  Title Childhood asthma after bacterial colonization of the airway in neonates Type Journal Article
  Year 2007 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 357 Issue 15 Pages 1487-1495  
  Keywords Asthma/drug therapy/immunology/*microbiology; Bacterial Infections/*complications/immunology; Bronchodilator Agents/therapeutic use; Budesonide/therapeutic use; Child, Preschool; Cohort Studies; Female; Haemophilus influenzae/isolation & purification; Humans; Hypersensitivity/microbiology; Hypopharynx/*microbiology; Immunoglobulin E/blood; Infant; Infant, Newborn; Kaplan-Meier Estimate; Male; Moraxella (Branhamella) catarrhalis/isolation & purification; Neutrophils/physiology; Respiratory Sounds/*etiology; Respiratory Tract Infections/*complications; Risk Factors; Staphylococcus aureus/isolation & purification; Streptococcus pneumoniae/isolation & purification  
  Abstract BACKGROUND: Pathological features of the airway in young children with severe recurrent wheeze suggest an association between bacterial colonization and the initiating events of early asthma. We conducted a study to investigate a possible association between bacterial colonization of the hypopharynx in asymptomatic neonates and later development of recurrent wheeze, asthma, and allergy during the first 5 years of life. METHODS: The subjects were children from the Copenhagen Prospective Study on Asthma in Childhood birth cohort who were born to mothers with asthma. Aspirates from the hypopharyngeal region of asymptomatic 1-month-old infants were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Wheeze was monitored prospectively on diary cards during the first 5 years of life. Blood eosinophil count and total IgE and specific IgE were measured at 4 years of age. Lung function was measured and asthma was diagnosed at 5 years of age. RESULTS: Hypopharyngeal samples were cultured from 321 neonates at 1 month of age. Twenty-one percent of the infants were colonized with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms; colonization with one or more of these organisms, but not colonization with S. aureus, was significantly associated with persistent wheeze (hazard ratio, 2.40; 95% confidence interval [CI], 1.45 to 3.99), acute severe exacerbation of wheeze (hazard ratio, 2.99; 95% CI, 1.66 to 5.39), and hospitalization for wheeze (hazard ratio, 3.85; 95% CI, 1.90 to 7.79). Blood eosinophil counts and total IgE at 4 years of age were significantly increased in children colonized neonatally with S. pneumoniae, M. catarrhalis, H. influenzae, or a combination of these organisms, but specific IgE was not significantly affected. The prevalence of asthma and the reversibility of airway resistance after beta2-agonist administration at 5 years of age were significantly increased in the children colonized neonatally with these organisms as compared with the children without such colonization (33% vs. 10% and 23% vs. 18%, respectively). CONCLUSIONS: Neonates colonized in the hypopharyngeal region with S. pneumoniae, H. influenzae, or M. catarrhalis, or with a combination of these organisms, are at increased risk for recurrent wheeze and asthma early in life.  
  Address Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen. bisgaard@copsac.dk  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Pipper, C.B.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:17928596 Approved no  
  Call Number Serial 116  
Permanent link to this record
 

 
Author Bisgaard, H.; Hermansen, M.N.; Loland, L.; Halkjaer, L.B.; Buchvald, F. url  doi
openurl 
  Title Intermittent inhaled corticosteroids in infants with episodic wheezing Type Journal Article
  Year 2006 Publication The New England Journal of Medicine Abbreviated Journal N Engl J Med  
  Volume 354 Issue 19 Pages 1998-2005  
  Keywords Administration, Inhalation; Asthma/*prevention & control; Bronchodilator Agents/*administration & dosage; Budesonide/*administration & dosage; Disease Progression; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Prospective Studies; Respiratory Sounds/*drug effects; Risk Factors; Treatment Failure  
  Abstract BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study. RESULTS: We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group (absolute difference, 1 percent; 95 percent confidence interval, -4.8 to 6.9 percent). Twenty-four percent of children in the budesonide group had persistent wheezing, as compared with 21 percent in the placebo group (hazard ratio, 1.22; 95 percent confidence interval, 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis. The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status. Height and bone mineral density were not affected by treatment. CONCLUSIONS: Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. (ClinicalTrials.gov number, NCT00234390.).  
  Address Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen  
  Corporate Author Thesis  
  Impact Factor (down) 55,873 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Buchvald, F.  
  ISSN 0028-4793 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:16687712 Approved no  
  Call Number Serial 194  
Permanent link to this record
 

 
Author Bisgaard, H.; Szefler, S. url  doi
openurl 
  Title Long-acting beta2 agonists and paediatric asthma Type Journal Article
  Year 2006 Publication Lancet Abbreviated Journal Lancet  
  Volume 367 Issue 9507 Pages 286-288  
  Keywords Adolescent; Adrenergic beta-Agonists/*therapeutic use; Asthma/*drug therapy; Child; Child, Preschool; Humans; *Pediatrics; *Product Surveillance, Postmarketing  
  Abstract  
  Address Danish Paediatric Asthma Centre, Copenhagen, University Hospital, DK-2900 Gentofte, Copenhagen, Denmark. Bisgaard@copsac.dk  
  Corporate Author Thesis  
  Impact Factor (down) 45,217 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Szefler, S.  
  ISSN 0140-6736 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:16443026 Approved no  
  Call Number Serial 189  
Permanent link to this record
 

 
Author Bisgaard, H.; Munck, S.L.; Nielsen, J.P.; Petersen, W.; Ohlsson, S.V. url  openurl
  Title Inhaled budesonide for treatment of recurrent wheezing in early childhood Type
  Year 1990 Publication Lancet Abbreviated Journal Lancet  
  Volume 336 Issue 8716 Pages 649-651  
  Keywords Administration, Inhalation; Administration, Oral; Aerosols; Budesonide; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Female; Glucocorticoids/*administration & dosage/therapeutic use; Humans; Infant; Male; Masks; Multicenter Studies as Topic; Pregnenediones/*administration & dosage/therapeutic use; Randomized Controlled Trials as Topic; Recurrence; Respiratory Sounds/*drug effects; Time Factors  
  Abstract 77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols were inhaled from a spacer with a facemask. Budesonide significantly improved symptom scores of wheezing, sleep disturbance, and patient happiness. The frequency of severe exacerbations that required a course of oral prednisolone was also significantly reduced. The treatment effect appeared to be fully established after 6-8 weeks and no side-effects could be ascribed to the active treatment. The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask. Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe recurrent wheeze and dyspnoea, and possibly reduce their requirement for oral steroids.  
  Address Department of Paediatrics, University Hospital of Copenhagen, Denmark  
  Corporate Author Thesis  
  Impact Factor (down) 45,217 First Author Bisgaard, H. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Ohlsson, S.V.  
  ISSN 0140-6736 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:1975851 Approved no  
  Call Number Serial 243  
Permanent link to this record
 

 
Author Horikoshi, M.; Beaumont, R.N.; Day, F.R.; Warrington, N.M.; Kooijman, M.N.; Fernandez-Tajes, J.; Feenstra, B.; van Zuydam, N.R.; Gaulton, K.J.; Grarup, N.; Bradfield, J.P.; Strachan, D.P.; Li-Gao, R.; Ahluwalia, T.S.; Kreiner, E.; Rueedi, R.; Lyytikainen, L.-P.; Cousminer, D.L.; Wu, Y.; Thiering, E.; Wang, C.A.; Have, C.T.; Hottenga, J.-J.; Vilor-Tejedor, N.; Joshi, P.K.; Boh, E.T.H.; Ntalla, I.; Pitkanen, N.; Mahajan, A.; van Leeuwen, E.M.; Joro, R.; Lagou, V.; Nodzenski, M.; Diver, L.A.; Zondervan, K.T.; Bustamante, M.; Marques-Vidal, P.; Mercader, J.M.; Bennett, A.J.; Rahmioglu, N.; Nyholt, D.R.; Ma, R.C.W.; Tam, C.H.T.; Tam, W.H.; Ganesh, S.K.; van Rooij, F.J.A.; Jones, S.E.; Loh, P.-R.; Ruth, K.S.; Tuke, M.A.; Tyrrell, J.; Wood, A.R.; Yaghootkar, H.; Scholtens, D.M.; Paternoster, L.; Prokopenko, I.; Kovacs, P.; Atalay, M.; Willems, S.M.; Panoutsopoulou, K.; Wang, X.; Carstensen, L.; Geller, F.; Schraut, K.E.; Murcia, M.; van Beijsterveldt, C.E.M.; Willemsen, G.; Appel, E.V.R.; Fonvig, C.E.; Trier, C.; Tiesler, C.M.T.; Standl, M.; Kutalik, Z.; Bonas-Guarch, S.; Hougaard, D.M.; Sanchez, F.; Torrents, D.; Waage, J.; Hollegaard, M.V.; de Haan, H.G.; Rosendaal, F.R.; Medina-Gomez, C.; Ring, S.M.; Hemani, G.; McMahon, G.; Robertson, N.R.; Groves, C.J.; Langenberg, C.; Luan, J.'an; Scott, R.A.; Zhao, J.H.; Mentch, F.D.; MacKenzie, S.M.; Reynolds, R.M.; Lowe, W.L.; Tonjes, A.; Stumvoll, M.; Lindi, V.; Lakka, T.A.; van Duijn, C.M.; Kiess, W.; Korner, A.; Sorensen, T.I.A.; Niinikoski, H.; Pahkala, K.; Raitakari, O.T.; Zeggini, E.; Dedoussis, G.V.; Teo, Y.-Y.; Saw, S.-M.; Melbye, M.; Campbell, H.; Wilson, J.F.; Vrijheid, M.; de Geus, E.J.C.N.; Boomsma, D.I.; Kadarmideen, H.N.; Holm, J.-C.; Hansen, T.; Sebert, S.; Hattersley, A.T.; Beilin, L.J.; Newnham, J.P.; Pennell, C.E.; Heinrich, J.; Adair, L.S.; Borja, J.B.; Mohlke, K.L.; Eriksson, J.G.; Widen, E.; Kahonen, M.; Viikari, J.S.; Lehtimaki, T.; Vollenweider, P.; Bonnelykke, K.; Bisgaard, H.; Mook-Kanamori, D.O.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; Pisinger, C.; Pedersen, O.; Power, C.; Hypponen, E.; Wareham, N.J.; Hakonarson, H.; Davies, E.; Walker, B.R.; Jaddoe, V.W.V.; Jarvelin, M.-R.; Grant, S.F.A.; Vaag, A.A.; Lawlor, D.A.; Frayling, T.M.; Smith, G.D.; Morris, A.P.; Ong, K.K.; Felix, J.F.; Timpson, N.J.; Perry, J.R.B.; Evans, D.M.; McCarthy, M.I.; Freathy, R.M. url  doi
openurl 
  Title Genome-wide associations for birth weight and correlations with adult disease Type Journal Article
  Year 2016 Publication Nature Abbreviated Journal Nature  
  Volume 538 Issue 7624 Pages 248-252  
  Keywords  
  Abstract Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 x 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 x 10-13), T2D (Rg = -0.27, P = 1.1 x 10-6) and coronary artery disease (Rg = -0.30, P = 6.5 x 10-9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 x 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.  
  Address Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol BS8 2BN, UK  
  Corporate Author Early Growth Genetics (EGG) Consortium Thesis  
  Impact Factor (down) 41,456 First Author Horikoshi, M. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Freathy, R.M.  
  ISSN 0028-0836 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27680694 Approved no  
  Call Number Serial 333  
Permanent link to this record
 

 
Author Okbay, A.; Beauchamp, J.P.; Fontana, M.A.; Lee, J.J.; Pers, T.H.; Rietveld, C.A.; Turley, P.; Chen, G.-B.; Emilsson, V.; Meddens, S.F.W.; Oskarsson, S.; Pickrell, J.K.; Thom, K.; Timshel, P.; de Vlaming, R.; Abdellaoui, A.; Ahluwalia, T.S.; Bacelis, J.; Baumbach, C.; Bjornsdottir, G.; Brandsma, J.H.; Pina Concas, M.; Derringer, J.; Furlotte, N.A.; Galesloot, T.E.; Girotto, G.; Gupta, R.; Hall, L.M.; Harris, S.E.; Hofer, E.; Horikoshi, M.; Huffman, J.E.; Kaasik, K.; Kalafati, I.P.; Karlsson, R.; Kong, A.; Lahti, J.; van der Lee, S.J.; deLeeuw, C.; Lind, P.A.; Lindgren, K.-O.; Liu, T.; Mangino, M.; Marten, J.; Mihailov, E.; Miller, M.B.; van der Most, P.J.; Oldmeadow, C.; Payton, A.; Pervjakova, N.; Peyrot, W.J.; Qian, Y.; Raitakari, O.; Rueedi, R.; Salvi, E.; Schmidt, B.; Schraut, K.E.; Shi, J.; Smith, A.V.; Poot, R.A.; St Pourcain, B.; Teumer, A.; Thorleifsson, G.; Verweij, N.; Vuckovic, D.; Wellmann, J.; Westra, H.-J.; Yang, J.; Zhao, W.; Zhu, Z.; Alizadeh, B.Z.; Amin, N.; Bakshi, A.; Baumeister, S.E.; Biino, G.; Bonnelykke, K.; Boyle, P.A.; Campbell, H.; Cappuccio, F.P.; Davies, G.; De Neve, J.-E.; Deloukas, P.; Demuth, I.; Ding, J.; Eibich, P.; Eisele, L.; Eklund, N.; Evans, D.M.; Faul, J.D.; Feitosa, M.F.; Forstner, A.J.; Gandin, I.; Gunnarsson, B.; Halldorsson, B.V.; Harris, T.B.; Heath, A.C.; Hocking, L.J.; Holliday, E.G.; Homuth, G.; Horan, M.A.; Hottenga, J.-J.; de Jager, P.L.; Joshi, P.K.; Jugessur, A.; Kaakinen, M.A.; Kahonen, M.; Kanoni, S.; Keltigangas-Jarvinen, L.; Kiemeney, L.A.L.M.; Kolcic, I.; Koskinen, S.; Kraja, A.T.; Kroh, M.; Kutalik, Z.; Latvala, A.; Launer, L.J.; Lebreton, M.P.; Levinson, D.F.; Lichtenstein, P.; Lichtner, P.; Liewald, D.C.M.; Loukola, A.; Madden, P.A.; Magi, R.; Maki-Opas, T.; Marioni, R.E.; Marques-Vidal, P.; Meddens, G.A.; McMahon, G.; Meisinger, C.; Meitinger, T.; Milaneschi, Y.; Milani, L.; Montgomery, G.W.; Myhre, R.; Nelson, C.P.; Nyholt, D.R.; Ollier, W.E.R.; Palotie, A.; Paternoster, L.; Pedersen, N.L.; Petrovic, K.E.; Porteous, D.J.; Raikkonen, K.; Ring, S.M.; Robino, A.; Rostapshova, O.; Rudan, I.; Rustichini, A.; Salomaa, V.; Sanders, A.R.; Sarin, A.-P.; Schmidt, H.; Scott, R.J.; Smith, B.H.; Smith, J.A.; Staessen, J.A.; Steinhagen-Thiessen, E.; Strauch, K.; Terracciano, A.; Tobin, M.D.; Ulivi, S.; Vaccargiu, S.; Quaye, L.; van Rooij, F.J.A.; Venturini, C.; Vinkhuyzen, A.A.E.; Volker, U.; Volzke, H.; Vonk, J.M.; Vozzi, D.; Waage, J.; Ware, E.B.; Willemsen, G.; Attia, J.R.; Bennett, D.A.; Berger, K.; Bertram, L.; Bisgaard, H.; Boomsma, D.I.; Borecki, I.B.; Bultmann, U.; Chabris, C.F.; Cucca, F.; Cusi, D.; Deary, I.J.; Dedoussis, G.V.; van Duijn, C.M.; Eriksson, J.G.; Franke, B.; Franke, L.; Gasparini, P.; Gejman, P.V.; Gieger, C.; Grabe, H.-J.; Gratten, J.; Groenen, P.J.F.; Gudnason, V.; van der Harst, P.; Hayward, C.; Hinds, D.A.; Hoffmann, W.; Hypponen, E.; Iacono, W.G.; Jacobsson, B.; Jarvelin, M.-R.; Jockel, K.-H.; Kaprio, J.; Kardia, S.L.R.; Lehtimaki, T.; Lehrer, S.F.; Magnusson, P.K.E.; Martin, N.G.; McGue, M.; Metspalu, A.; Pendleton, N.; Penninx, B.W.J.H.; Perola, M.; Pirastu, N.; Pirastu, M.; Polasek, O.; Posthuma, D.; Power, C.; Province, M.A.; Samani, N.J.; Schlessinger, D.; Schmidt, R.; Sorensen, T.I.A.; Spector, T.D.; Stefansson, K.; Thorsteinsdottir, U.; Thurik, A.R.; Timpson, N.J.; Tiemeier, H.; Tung, J.Y.; Uitterlinden, A.G.; Vitart, V.; Vollenweider, P.; Weir, D.R.; Wilson, J.F.; Wright, A.F.; Conley, D.C.; Krueger, R.F.; Davey Smith, G.; Hofman, A.; Laibson, D.I.; Medland, S.E.; Meyer, M.N.; Yang, J.; Johannesson, M.; Visscher, P.M.; Esko, T.; Koellinger, P.D.; Cesarini, D.; Benjamin, D.J. url  doi
openurl 
  Title Genome-wide association study identifies 74 loci associated with educational attainment Type Journal Article
  Year 2016 Publication Nature Abbreviated Journal Nature  
  Volume 533 Issue 7604 Pages 539-542  
  Keywords  
  Abstract Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.  
  Address Center for Economic and Social Research, University of Southern California, Los Angeles, California 90089-3332, USA  
  Corporate Author LifeLines Cohort Study Thesis  
  Impact Factor (down) 41,456 First Author Okbay, A Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Benjamin, D.J.  
  ISSN 0028-0836 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27225129 Approved no  
  Call Number Serial 321  
Permanent link to this record
 

 
Author Joshi, P.K.; Esko, T.; Mattsson, H.; Eklund, N.; Gandin, I.; Nutile, T.; Jackson, A.U.; Schurmann, C.; Smith, A.V.; Zhang, W.; Okada, Y.; Stancakova, A.; Faul, J.D.; Zhao, W.; Bartz, T.M.; Concas, M.P.; Franceschini, N.; Enroth, S.; Vitart, V.; Trompet, S.; Guo, X.; Chasman, D.I.; O'Connel, J.R.; Corre, T.; Nongmaithem, S.S.; Chen, Y.; Mangino, M.; Ruggiero, D.; Traglia, M.; Farmaki, A.-E.; Kacprowski, T.; Bjonnes, A.; van der Spek, A.; Wu, Y.; Giri, A.K.; Yanek, L.R.; Wang, L.; Hofer, E.; Rietveld, C.A.; McLeod, O.; Cornelis, M.C.; Pattaro, C.; Verweij, N.; Baumbach, C.; Abdellaoui, A.; Warren, H.R.; Vuckovic, D.; Mei, H.; Bouchard, C.; Perry, J.R.B.; Cappellani, S.; Mirza, S.S.; Benton, M.C.; Broeckel, U.; Medland, S.E.; Lind, P.A.; Malerba, G.; Drong, A.; Yengo, L.; Bielak, L.F.; Zhi, D.; van der Most, P.J.; Shriner, D.; Magi, R.; Hemani, G.; Karaderi, T.; Wang, Z.; Liu, T.; Demuth, I.; Zhao, J.H.; Meng, W.; Lataniotis, L.; van der Laan, S.W.; Bradfield, J.P.; Wood, A.R.; Bonnefond, A.; Ahluwalia, T.S.; Hall, L.M.; Salvi, E.; Yazar, S.; Carstensen, L.; de Haan, H.G.; Abney, M.; Afzal, U.; Allison, M.A.; Amin, N.; Asselbergs, F.W.; Bakker, S.J.L.; Barr, R.G.; Baumeister, S.E.; Benjamin, D.J.; Bergmann, S.; Boerwinkle, E.; Bottinger, E.P.; Campbell, A.; Chakravarti, A.; Chan, Y.; Chanock, S.J.; Chen, C.; Chen, Y.-D.I.; Collins, F.S.; Connell, J.; Correa, A.; Cupples, L.A.; Smith, G.D.; Davies, G.; Dorr, M.; Ehret, G.; Ellis, S.B.; Feenstra, B.; Feitosa, M.F.; Ford, I.; Fox, C.S.; Frayling, T.M.; Friedrich, N.; Geller, F.; Scotland, G.; Gillham-Nasenya, I.; Gottesman, O.; Graff, M.; Grodstein, F.; Gu, C.; Haley, C.; Hammond, C.J.; Harris, S.E.; Harris, T.B.; Hastie, N.D.; Heard-Costa, N.L.; Heikkila, K.; Hocking, L.J.; Homuth, G.; Hottenga, J.-J.; Huang, J.; Huffman, J.E.; Hysi, P.G.; Ikram, M.A.; Ingelsson, E.; Joensuu, A.; Johansson, A.; Jousilahti, P.; Jukema, J.W.; Kahonen, M.; Kamatani, Y.; Kanoni, S.; Kerr, S.M.; Khan, N.M.; Koellinger, P.; Koistinen, H.A.; Kooner, M.K.; Kubo, M.; Kuusisto, J.; Lahti, J.; Launer, L.J.; Lea, R.A.; Lehne, B.; Lehtimaki, T.; Liewald, D.C.M.; Lind, L.; Loh, M.; Lokki, M.-L.; London, S.J.; Loomis, S.J.; Loukola, A.; Lu, Y.; Lumley, T.; Lundqvist, A.; Mannisto, S.; Marques-Vidal, P.; Masciullo, C.; Matchan, A.; Mathias, R.A.; Matsuda, K.; Meigs, J.B.; Meisinger, C.; Meitinger, T.; Menni, C.; Mentch, F.D.; Mihailov, E.; Milani, L.; Montasser, M.E.; Montgomery, G.W.; Morrison, A.; Myers, R.H.; Nadukuru, R.; Navarro, P.; Nelis, M.; Nieminen, M.S.; Nolte, I.M.; O'Connor, G.T.; Ogunniyi, A.; Padmanabhan, S.; Palmas, W.R.; Pankow, J.S.; Patarcic, I.; Pavani, F.; Peyser, P.A.; Pietilainen, K.; Poulter, N.; Prokopenko, I.; Ralhan, S.; Redmond, P.; Rich, S.S.; Rissanen, H.; Robino, A.; Rose, L.M.; Rose, R.; Sala, C.; Salako, B.; Salomaa, V.; Sarin, A.-P.; Saxena, R.; Schmidt, H.; Scott, L.J.; Scott, W.R.; Sennblad, B.; Seshadri, S.; Sever, P.; Shrestha, S.; Smith, B.H.; Smith, J.A.; Soranzo, N.; Sotoodehnia, N.; Southam, L.; Stanton, A.V.; Stathopoulou, M.G.; Strauch, K.; Strawbridge, R.J.; Suderman, M.J.; Tandon, N.; Tang, S.-T.; Taylor, K.D.; Tayo, B.O.; Toglhofer, A.M.; Tomaszewski, M.; Tsernikova, N.; Tuomilehto, J.; Uitterlinden, A.G.; Vaidya, D.; van Hylckama Vlieg, A.; van Setten, J.; Vasankari, T.; Vedantam, S.; Vlachopoulou, E.; Vozzi, D.; Vuoksimaa, E.; Waldenberger, M.; Ware, E.B.; Wentworth-Shields, W.; Whitfield, J.B.; Wild, S.; Willemsen, G.; Yajnik, C.S.; Yao, J.; Zaza, G.; Zhu, X.; Salem, R.M.; Melbye, M.; Bisgaard, H.; Samani, N.J.; Cusi, D.; Mackey, D.A.; Cooper, R.S.; Froguel, P.; Pasterkamp, G.; Grant, S.F.A.; Hakonarson, H.; Ferrucci, L.; Scott, R.A.; Morris, A.D.; Palmer, C.N.A.; Dedoussis, G.; Deloukas, P.; Bertram, L.; Lindenberger, U.; Berndt, S.I.; Lindgren, C.M.; Timpson, N.J.; Tonjes, A.; Munroe, P.B.; Sorensen, T.I.A.; Rotimi, C.N.; Arnett, D.K.; Oldehinkel, A.J.; Kardia, S.L.R.; Balkau, B.; Gambaro, G.; Morris, A.P.; Eriksson, J.G.; Wright, M.J.; Martin, N.G.; Hunt, S.C.; Starr, J.M.; Deary, I.J.; Griffiths, L.R.; Tiemeier, H.; Pirastu, N.; Kaprio, J.; Wareham, N.J.; Perusse, L.; Wilson, J.G.; Girotto, G.; Caulfield, M.J.; Raitakari, O.; Boomsma, D.I.; Gieger, C.; van der Harst, P.; Hicks, A.A.; Kraft, P.; Sinisalo, J.; Knekt, P.; Johannesson, M.; Magnusson, P.K.E.; Hamsten, A.; Schmidt, R.; Borecki, I.B.; Vartiainen, E.; Becker, D.M.; Bharadwaj, D.; Mohlke, K.L.; Boehnke, M.; van Duijn, C.M.; Sanghera, D.K.; Teumer, A.; Zeggini, E.; Metspalu, A.; Gasparini, P.; Ulivi, S.; Ober, C.; Toniolo, D.; Rudan, I.; Porteous, D.J.; Ciullo, M.; Spector, T.D.; Hayward, C.; Dupuis, J.; Loos, R.J.F.; Wright, A.F.; Chandak, G.R.; Vollenweider, P.; Shuldiner, A.R.; Ridker, P.M.; Rotter, J.I.; Sattar, N.; Gyllensten, U.; North, K.E.; Pirastu, M.; Psaty, B.M.; Weir, D.R.; Laakso, M.; Gudnason, V.; Takahashi, A.; Chambers, J.C.; Kooner, J.S.; Strachan, D.P.; Campbell, H.; Hirschhorn, J.N.; Perola, M.; Polasek, O.; Wilson, J.F. url  doi
openurl 
  Title Directional dominance on stature and cognition in diverse human populations Type Journal Article
  Year 2015 Publication Nature Abbreviated Journal Nature  
  Volume 523 Issue 7561 Pages 459-462  
  Keywords Biological Evolution; Blood Pressure/genetics; Body Height/*genetics; Cholesterol, LDL/genetics; *Cognition; Cohort Studies; Educational Status; Female; Forced Expiratory Volume/genetics; Genome, Human/genetics; *Homozygote; Humans; Lung Volume Measurements; Male; Phenotype  
  Abstract Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 x 10(-300), 2.1 x 10(-6), 2.5 x 10(-10) and 1.8 x 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.  
  Address 1] Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. [2] MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, EH4 2XU Edinburgh, UK  
  Corporate Author BioBank Japan Project Thesis  
  Impact Factor (down) 41,456 First Author Joshi, P.K. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Wilson, J.F.  
  ISSN 0028-0836 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26131930; PMCID:PMC4516141 Approved no  
  Call Number Serial 35  
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Author Tyrrell, J.; Richmond, R.C.; Palmer, T.M.; Feenstra, B.; Rangarajan, J.; Metrustry, S.; Cavadino, A.; Paternoster, L.; Armstrong, L.L.; De Silva, N.M.G.; Wood, A.R.; Horikoshi, M.; Geller, F.; Myhre, R.; Bradfield, J.P.; Kreiner-Moller, E.; Huikari, V.; Painter, J.N.; Hottenga, J.-J.; Allard, C.; Berry, D.J.; Bouchard, L.; Das, S.; Evans, D.M.; Hakonarson, H.; Hayes, M.G.; Heikkinen, J.; Hofman, A.; Knight, B.; Lind, P.A.; McCarthy, M.I.; McMahon, G.; Medland, S.E.; Melbye, M.; Morris, A.P.; Nodzenski, M.; Reichetzeder, C.; Ring, S.M.; Sebert, S.; Sengpiel, V.; Sorensen, T.I.A.; Willemsen, G.; de Geus, E.J.C.; Martin, N.G.; Spector, T.D.; Power, C.; Jarvelin, M.-R.; Bisgaard, H.; Grant, S.F.A.; Nohr, E.A.; Jaddoe, V.W.; Jacobsson, B.; Murray, J.C.; Hocher, B.; Hattersley, A.T.; Scholtens, D.M.; Davey Smith, G.; Hivert, M.-F.; Felix, J.F.; Hypponen, E.; Lowe, W.L.J.; Frayling, T.M.; Lawlor, D.A.; Freathy, R.M. url  doi
openurl 
  Title Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight Type Journal Article
  Year 2016 Publication JAMA Abbreviated Journal Jama  
  Volume 315 Issue 11 Pages 1129-1140  
  Keywords  
  Abstract IMPORTANCE: Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. OBJECTIVE: To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. DESIGN, SETTING, AND PARTICIPANTS: Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. EXPOSURES: Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. MAIN OUTCOME AND MEASURE: Offspring birth weight from 18 studies. RESULTS: Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 x 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1x10(-5)), respectively. A 1-SD ( approximately 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( approximately 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( approximately 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. CONCLUSIONS AND RELEVANCE: In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.  
  Address Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom5Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom  
  Corporate Author Early Growth Genetics (EGG) Consortium Thesis  
  Impact Factor (down) 35,289 First Author Tyrrell, J. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Freathy, R.M.  
  ISSN 0098-7484 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26978208 Approved no  
  Call Number Serial 310  
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Author Chawes, B.L.; Bonnelykke, K.; Stokholm, J.; Vissing, N.H.; Bjarnadottir, E.; Schoos, A.-M.M.; Wolsk, H.M.; Pedersen, T.M.; Vinding, R.K.; Thorsteinsdottir, S.; Arianto, L.; Hallas, H.W.; Heickendorff, L.; Brix, S.; Rasmussen, M.A.; Bisgaard, H. url  doi
openurl 
  Title Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial Type Journal Article
  Year 2016 Publication JAMA Abbreviated Journal Jama  
  Volume 315 Issue 4 Pages 353-361  
  Keywords Adult; Asthma/diagnosis/prevention & control; Child, Preschool; Cholecalciferol/*administration & dosage; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Trimester, Third; *Respiratory Sounds; Vitamin D/analogs & derivatives/blood; Vitamins/*administration & dosage  
  Abstract IMPORTANCE: Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE: To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS: Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES: Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS: Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. [table: see text]. CONCLUSIONS AND RELEVANCE: The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00856947.  
  Address Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark  
  Corporate Author Thesis  
  Impact Factor (down) 35,289 First Author Chawes, B.L Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bisgaard, H.  
  ISSN 0098-7484 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26813208 Approved no  
  Call Number Serial 15  
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Author Barban, N.; Jansen, R.; de Vlaming, R.; Vaez, A.; Mandemakers, J.J.; Tropf, F.C.; Shen, X.; Wilson, J.F.; Chasman, D.I.; Nolte, I.M.; Tragante, V.; van der Laan, S.W.; Perry, J.R.B.; Kong, A.; Ahluwalia, T.S.; Albrecht, E.; Yerges-Armstrong, L.; Atzmon, G.; Auro, K.; Ayers, K.; Bakshi, A.; Ben-Avraham, D.; Berger, K.; Bergman, A.; Bertram, L.; Bielak, L.F.; Bjornsdottir, G.; Bonder, M.J.; Broer, L.; Bui, M.; Barbieri, C.; Cavadino, A.; Chavarro, J.E.; Turman, C.; Concas, M.P.; Cordell, H.J.; Davies, G.; Eibich, P.; Eriksson, N.; Esko, T.; Eriksson, J.; Falahi, F.; Felix, J.F.; Fontana, M.A.; Franke, L.; Gandin, I.; Gaskins, A.J.; Gieger, C.; Gunderson, E.P.; Guo, X.; Hayward, C.; He, C.; Hofer, E.; Huang, H.; Joshi, P.K.; Kanoni, S.; Karlsson, R.; Kiechl, S.; Kifley, A.; Kluttig, A.; Kraft, P.; Lagou, V.; Lecoeur, C.; Lahti, J.; Li-Gao, R.; Lind, P.A.; Liu, T.; Makalic, E.; Mamasoula, C.; Matteson, L.; Mbarek, H.; McArdle, P.F.; McMahon, G.; Meddens, S.F.W.; Mihailov, E.; Miller, M.; Missmer, S.A.; Monnereau, C.; van der Most, P.J.; Myhre, R.; Nalls, M.A.; Nutile, T.; Kalafati, I.P.; Porcu, E.; Prokopenko, I.; Rajan, K.B.; Rich-Edwards, J.; Rietveld, C.A.; Robino, A.; Rose, L.M.; Rueedi, R.; Ryan, K.A.; Saba, Y.; Schmidt, D.; Smith, J.A.; Stolk, L.; Streeten, E.; Tonjes, A.; Thorleifsson, G.; Ulivi, S.; Wedenoja, J.; Wellmann, J.; Willeit, P.; Yao, J.; Yengo, L.; Zhao, J.H.; Zhao, W.; Zhernakova, D.V.; Amin, N.; Andrews, H.; Balkau, B.; Barzilai, N.; Bergmann, S.; Biino, G.; Bisgaard, H.; Bonnelykke, K.; Boomsma, D.I.; Buring, J.E.; Campbell, H.; Cappellani, S.; Ciullo, M.; Cox, S.R.; Cucca, F.; Toniolo, D.; Davey-Smith, G.; Deary, I.J.; Dedoussis, G.; Deloukas, P.; van Duijn, C.M.; de Geus, E.J.C.; Eriksson, J.G.; Evans, D.A.; Faul, J.D.; Sala, C.F.; Froguel, P.; Gasparini, P.; Girotto, G.; Grabe, H.-J.; Greiser, K.H.; Groenen, P.J.F.; de Haan, H.G.; Haerting, J.; Harris, T.B.; Heath, A.C.; Heikkila, K.; Hofman, A.; Homuth, G.; Holliday, E.G.; Hopper, J.; Hypponen, E.; Jacobsson, B.; Jaddoe, V.W.V.; Johannesson, M.; Jugessur, A.; Kahonen, M.; Kajantie, E.; Kardia, S.L.R.; Keavney, B.; Kolcic, I.; Koponen, P.; Kovacs, P.; Kronenberg, F.; Kutalik, Z.; La Bianca, M.; Lachance, G.; Iacono, W.G.; Lai, S.; Lehtimaki, T.; Liewald, D.C.; Lindgren, C.M.; Liu, Y.; Luben, R.; Lucht, M.; Luoto, R.; Magnus, P.; Magnusson, P.K.E.; Martin, N.G.; McGue, M.; McQuillan, R.; Medland, S.E.; Meisinger, C.; Mellstrom, D.; Metspalu, A.; Traglia, M.; Milani, L.; Mitchell, P.; Montgomery, G.W.; Mook-Kanamori, D.; de Mutsert, R.; Nohr, E.A.; Ohlsson, C.; Olsen, J.; Ong, K.K.; Paternoster, L.; Pattie, A.; Penninx, B.W.J.H.; Perola, M.; Peyser, P.A.; Pirastu, M.; Polasek, O.; Power, C.; Kaprio, J.; Raffel, L.J.; Raikkonen, K.; Raitakari, O.; Ridker, P.M.; Ring, S.M.; Roll, K.; Rudan, I.; Ruggiero, D.; Rujescu, D.; Salomaa, V.; Schlessinger, D.; Schmidt, H.; Schmidt, R.; Schupf, N.; Smit, J.; Sorice, R.; Spector, T.D.; Starr, J.M.; Stockl, D.; Strauch, K.; Stumvoll, M.; Swertz, M.A.; Thorsteinsdottir, U.; Thurik, A.R.; Timpson, N.J.; Tung, J.Y.; Uitterlinden, A.G.; Vaccargiu, S.; Viikari, J.; Vitart, V.; Volzke, H.; Vollenweider, P.; Vuckovic, D.; Waage, J.; Wagner, G.G.; Wang, J.J.; Wareham, N.J.; Weir, D.R.; Willemsen, G.; Willeit, J.; Wright, A.F.; Zondervan, K.T.; Stefansson, K.; Krueger, R.F.; Lee, J.J.; Benjamin, D.J.; Cesarini, D.; Koellinger, P.D.; den Hoed, M.; Snieder, H.; Mills, M.C. url  doi
openurl 
  Title Genome-wide analysis identifies 12 loci influencing human reproductive behavior Type Journal Article
  Year 2016 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 48 Issue 12 Pages 1462-1472  
  Keywords *Birth Order; Female; Fertility/genetics; *Genome-Wide Association Study; Humans; Maternal Age; Parity/*genetics; Phenotype; Polymorphism, Single Nucleotide/genetics; Pregnancy; *Quantitative Trait Loci; Reproduction/*genetics; Reproductive Behavior/*physiology  
  Abstract The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.  
  Address Department of Sociology and Nuffield College, University of Oxford, Oxford, UK  
  Corporate Author LifeLines Cohort Study Thesis  
  Impact Factor (down) 31,616 First Author Barban, N. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Mills, MC.  
  ISSN 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27798627 Approved no  
  Call Number Serial 353  
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Author Paternoster, L.; Standl, M.; Waage, J.; Baurecht, H.; Hotze, M.; Strachan, D.P.; Curtin, J.A.; Bonnelykke, K.; Tian, C.; Takahashi, A.; Esparza-Gordillo, J.; Alves, A.C.; Thyssen, J.P.; den Dekker, H.T.; Ferreira, M.A.; Altmaier, E.; Sleiman, P.M.A.; Xiao, F.L.; Gonzalez, J.R.; Marenholz, I.; Kalb, B.; Pino-Yanes, M.; Xu, C.-J.; Carstensen, L.; Groen-Blokhuis, M.M.; Venturini, C.; Pennell, C.E.; Barton, S.J.; Levin, A.M.; Curjuric, I.; Bustamante, M.; Kreiner-Moller, E.; Lockett, G.A.; Bacelis, J.; Bunyavanich, S.; Myers, R.A.; Matanovic, A.; Kumar, A.; Tung, J.Y.; Hirota, T.; Kubo, M.; McArdle, W.L.; Henderson, A.J.; Kemp, J.P.; Zheng, J.; Smith, G.D.; Ruschendorf, F.; Bauerfeind, A.; Lee-Kirsch, M.A.; Arnold, A.; Homuth, G.; Schmidt, C.O.; Mangold, E.; Cichon, S.; Keil, T.; Rodriguez, E.; Peters, A.; Franke, A.; Lieb, W.; Novak, N.; Folster-Holst, R.; Horikoshi, M.; Pekkanen, J.; Sebert, S.; Husemoen, L.L.; Grarup, N.; de Jongste, J.C.; Rivadeneira, F.; Hofman, A.; Jaddoe, V.W.V.; Pasmans, S.G.M.A.; Elbert, N.J.; Uitterlinden, A.G.; Marks, G.B.; Thompson, P.J.; Matheson, M.C.; Robertson, C.F.; Ried, J.S.; Li, J.; Zuo, X.B.; Zheng, X.D.; Yin, X.Y.; Sun, L.D.; McAleer, M.A.; O'Regan, G.M.; Fahy, C.M.R.; Campbell, L.E.; Macek, M.; Kurek, M.; Hu, D.; Eng, C.; Postma, D.S.; Feenstra, B.; Geller, F.; Hottenga, J.J.; Middeldorp, C.M.; Hysi, P.; Bataille, V.; Spector, T.; Tiesler, C.M.T.; Thiering, E.; Pahukasahasram, B.; Yang, J.J.; Imboden, M.; Huntsman, S.; Vilor-Tejedor, N.; Relton, C.L.; Myhre, R.; Nystad, W.; Custovic, A.; Weiss, S.T.; Meyers, D.A.; Soderhall, C.; Melen, E.; Ober, C.; Raby, B.A.; Simpson, A.; Jacobsson, B.; Holloway, J.W.; Bisgaard, H.; Sunyer, J.; Probst-Hensch, N.M.; Williams, L.K.; Godfrey, K.M.; Wang, C.A.; Boomsma, D.I.; Melbye, M.; Koppelman, G.H.; Jarvis, D.; McLean, W.H.I.; Irvine, A.D.; Zhang, X.J.; Hakonarson, H.; Gieger, C.; Burchard, E.G.; Martin, N.G.; Duijts, L.; Linneberg, A.; Jarvelin, M.-R.; Nothen, M.M.; Lau, S.; Hubner, N.; Lee, Y.-A.; Tamari, M.; Hinds, D.A.; Glass, D.; Brown, S.J.; Heinrich, J.; Evans, D.M.; Weidinger, S. url  doi
openurl 
  Title Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis Type Journal Article
  Year 2015 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 47 Issue 12 Pages 1449-1456  
  Keywords  
  Abstract Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.  
  Address  
  Corporate Author EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium Thesis  
  Impact Factor (down) 29,352 First Author Paternoster, L. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Weidinger, S.  
  ISSN 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26482879; PMCID:PMC4753676 Approved no  
  Call Number Serial 320  
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Author Bonnelykke, K.; Sleiman, P.; Nielsen, K.; Kreiner-Moller, E.; Mercader, J.M.; Belgrave, D.; den Dekker, H.T.; Husby, A.; Sevelsted, A.; Faura-Tellez, G.; Mortensen, L.J.; Paternoster, L.; Flaaten, R.; Molgaard, A.; Smart, D.E.; Thomsen, P.F.; Rasmussen, M.A.; Bonas-Guarch, S.; Holst, C.; Nohr, E.A.; Yadav, R.; March, M.E.; Blicher, T.; Lackie, P.M.; Jaddoe, V.W.V.; Simpson, A.; Holloway, J.W.; Duijts, L.; Custovic, A.; Davies, D.E.; Torrents, D.; Gupta, R.; Hollegaard, M.V.; Hougaard, D.M.; Hakonarson, H.; Bisgaard, H. url  doi
openurl 
  Title A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations Type Journal Article
  Year 2014 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 46 Issue 1 Pages 51-55  
  Keywords Asthma/etiology/*genetics; Cadherins/chemistry/*genetics/metabolism; Case-Control Studies; Child; Child, Preschool; Chromosomes, Human, Pair 17; DNA Repair Enzymes/genetics; DNA-Binding Proteins/genetics; Denmark; Female; *Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Interleukin-33; Interleukins/genetics; Male; Membrane Proteins/chemistry/*genetics/metabolism; Models, Molecular; Neoplasm Proteins/genetics; Polymorphism, Single Nucleotide; Protein Conformation; Receptors, Cell Surface/genetics  
  Abstract Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.  
  Address 1] Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. [2]  
  Corporate Author Thesis  
  Impact Factor (down) 29,352 First Author Bonnelykke, K. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Bisgaard, H.  
  ISSN 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24241537 Approved no  
  Call Number Serial 106  
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Author Bonnelykke, K.; Matheson, M.C.; Pers, T.H.; Granell, R.; Strachan, D.P.; Alves, A.C.; Linneberg, A.; Curtin, J.A.; Warrington, N.M.; Standl, M.; Kerkhof, M.; Jonsdottir, I.; Bukvic, B.K.; Kaakinen, M.; Sleimann, P.; Thorleifsson, G.; Thorsteinsdottir, U.; Schramm, K.; Baltic, S.; Kreiner-Moller, E.; Simpson, A.; St Pourcain, B.; Coin, L.; Hui, J.; Walters, E.H.; Tiesler, C.M.T.; Duffy, D.L.; Jones, G.; Ring, S.M.; McArdle, W.L.; Price, L.; Robertson, C.F.; Pekkanen, J.; Tang, C.S.; Thiering, E.; Montgomery, G.W.; Hartikainen, A.-L.; Dharmage, S.C.; Husemoen, L.L.; Herder, C.; Kemp, J.P.; Elliot, P.; James, A.; Waldenberger, M.; Abramson, M.J.; Fairfax, B.P.; Knight, J.C.; Gupta, R.; Thompson, P.J.; Holt, P.; Sly, P.; Hirschhorn, J.N.; Blekic, M.; Weidinger, S.; Hakonarsson, H.; Stefansson, K.; Heinrich, J.; Postma, D.S.; Custovic, A.; Pennell, C.E.; Jarvelin, M.-R.; Koppelman, G.H.; Timpson, N.; Ferreira, M.A.; Bisgaard, H.; Henderson, A.J. url  doi
openurl 
  Title Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization Type
  Year 2013 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 45 Issue 8 Pages 902-906  
  Keywords Alleles; Computational Biology; Gene Regulatory Networks; *Genetic Loci; *Genome-Wide Association Study; Genomics; Humans; Hypersensitivity/*genetics/metabolism; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Signal Transduction  
  Abstract Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.  
  Address COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark. kb@copsac.com  
  Corporate Author EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium Thesis  
  Impact Factor (down) 29,352 First Author Bonnelykke, K. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Henderson, A.J.  
  ISSN 1061-4036 ISBN