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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
Howe, Laurence J; Nivard, Michel G; Morris, Tim T; Hansen, Ailin F; Rasheed, Humaira; Cho, Yoonsu; Chittoor, Geetha; Ahlskog, Rafael; Lind, Penelope A; Palviainen, Teemu; van der Zee, Matthijs D; Cheesman, Rosa; Mangino, Massimo; Wang, Yunzhang; Li, Shuai; Klaric, Lucija; Ratliff, Scott M; Bielak, Lawrence F; Nygaard, Marianne; Giannelis, Alexandros; Willoughby, Emily A; Reynolds, Chandra A; Balbona, Jared V; Andreassen, Ole A; Ask, Helga; Baras, Aris; Bauer, Christopher R; Boomsma, Dorret I; Campbell, Archie; Campbell, Harry; Chen, Zhengming; Christofidou, Paraskevi; Corfield, Elizabeth; Dahm, Christina C; Dokuru, Deepika R; Evans, Luke M; de Geus, Eco J C; Giddaluru, Sudheer; Gordon, Scott D; Harden, K Paige; Hill, W David; Hughes, Amanda; Kerr, Shona M; Kim, Yongkang; Kweon, Hyeokmoon; Latvala, Antti; Lawlor, Deborah A; Li, Liming; Lin, Kuang; Magnus, Per.
Afiliação
  • Howe LJ; Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. laurence.howe@bristol.ac.uk.
  • Nivard MG; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. laurence.howe@bristol.ac.uk.
  • Morris TT; Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
  • Hansen AF; Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
  • Rasheed H; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Cho Y; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Chittoor G; Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
  • Ahlskog R; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • Lind PA; Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
  • Palviainen T; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • van der Zee MD; Department of Population Health Sciences, Geisinger Health, Danville, PA, USA.
  • Cheesman R; Department of Government, Uppsala University, Uppsala, Sweden.
  • Mangino M; Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Wang Y; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
  • Li S; Faculty of Medicine, University of Queensland, Brisbane, Australia.
  • Klaric L; Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
  • Ratliff SM; Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
  • Bielak LF; PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
  • Nygaard M; Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • Giannelis A; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Willoughby EA; NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
  • Reynolds CA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Balbona JV; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
  • Andreassen OA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Ask H; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  • Baras A; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
  • Bauer CR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Boomsma DI; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Campbell A; The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark.
  • Campbell H; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
  • Chen Z; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
  • Christofidou P; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
  • Corfield E; Department of Psychology, University of California, Riverside, Riverside, CA, USA.
  • Dahm CC; Department of Psychology & Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
  • Dokuru DR; Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
  • Evans LM; NORMENT Centre, University of Oslo, Oslo, Norway.
  • de Geus EJC; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Giddaluru S; Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
  • Gordon SD; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Harden KP; BioMarin Pharmaceutical Inc., Novato, CA, USA.
  • Hill WD; Biomedical and Translational Informatics, Geisinger Health, Danville, PA, USA.
  • Hughes A; Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
  • Kerr SM; Amsterdam Public Health (APH) and Amsterdam Reproduction and Development (AR&D), Amsterdam, the Netherlands.
  • Kim Y; Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
  • Kweon H; Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Latvala A; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Lawlor DA; MRC Population Health Research Unit, University of Oxford, Oxford, UK.
  • Li L; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Lin K; Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
  • Magnus P; Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
Nat Genet ; 54(5): 581-592, 2022 05.
Article em En | MEDLINE | ID: mdl-35534559
ABSTRACT
Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla Tipo de estudo: Clinical_trials / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla Tipo de estudo: Clinical_trials / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article