A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts
A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts
ABSTRACT The Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β=0.45, p=3.48×10?22), and using a significance level of p=0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR=2.17, 95% CI: 1.79-2.63, p=2.70×10?15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.
Lindstr?m Sara、Kraft Peter、Huang Hongyan、Aschard Hugues、Loomis Stephanie、Fuchs Charles、Chan Andrew T.、Hankinson Susan E.、Jensen Majken、Pasquale Louis R.、Rimm Eric、Tamimi Rulla M.、Wiggs Janey L.、Eliassen A. Heather、Tworoger Shelley S.、Kang Jae H.、Cornelis Marilyn、Turman Constance、Stampfer Meir J.、De Vivo Immaculata、Liang Liming、Kabrhel Christopher、Choi Hyon、Curhan Gary、Gaziano Michael、Huang Jinyan、Hunter David J.、Hu Frank
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public Health||Department of Epidemiology, University of WashingtonProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public Health||Department of Biostatistics, Harvard T.H. Chan School of Public HealthProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public HealthProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear InfirmaryChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical SchoolGastrointestinal Unit, Massachusetts General HospitalDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Department of Preventive Medicine, Northwestern University Feinberg School of Medicine||Department of Biostatistics and Epidemiology, University of MassachusettsChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Nutrition, Harvard T.H. Chan School of Public HealthDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Nutrition, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear InfirmaryDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Nutrition, Harvard T.H. Chan School of Public HealthProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public Health||Department of Biostatistics, Harvard T.H. Chan School of Public HealthChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Emergency Medicine, Center for Vascular Emergencies, Massachusetts General Hospital, Harvard Medical SchoolSection of Rheumatology and Clinical Epidemiology Unit, Boston University School of MedicineChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Renal Division, Department of Medicine, Brigham and Women's HospitalDivision of Aging, Department of Medicine, Brigham and Women's HospitalProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public HealthProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health||Department of Epidemiology, Harvard T.H. Chan School of Public Health||Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School||Department of Nutrition, Harvard T.H. Chan School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public Health||Department of Nutrition, Harvard T.H. Chan School of Public Health
医学研究方法基础医学遗传学
GWAScohortsimputationsecondary analysisassociation
Lindstr?m Sara,Kraft Peter,Huang Hongyan,Aschard Hugues,Loomis Stephanie,Fuchs Charles,Chan Andrew T.,Hankinson Susan E.,Jensen Majken,Pasquale Louis R.,Rimm Eric,Tamimi Rulla M.,Wiggs Janey L.,Eliassen A. Heather,Tworoger Shelley S.,Kang Jae H.,Cornelis Marilyn,Turman Constance,Stampfer Meir J.,De Vivo Immaculata,Liang Liming,Kabrhel Christopher,Choi Hyon,Curhan Gary,Gaziano Michael,Huang Jinyan,Hunter David J.,Hu Frank.A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/083030.点此复制
评论