Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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35534559
TITLE
Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
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.
© 2022. The Author(s).
DATE PUBLISHED
2022 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2021/03/05
accepted 2022/03/25
pubmed 2022/05/10 06:00
medline 2022/05/20 06:00
entrez 2022/05/09 23:20
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Howe LJ Howe Laurence J LJ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. laurence.howe@bristol.ac.uk.
Nivard MG Nivard Michel G MG Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
Morris TT Morris Tim T TT Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Hansen AF Hansen Ailin F AF K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Rasheed H Rasheed Humaira H K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Cho Y Cho Yoonsu Y Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Chittoor G Chittoor Geetha G Department of Population Health Sciences, Geisinger Health, Danville, PA, USA.
Ahlskog R Ahlskog Rafael R Department of Government, Uppsala University, Uppsala, Sweden.
Lind PA Lind Penelope A PA Faculty of Medicine, University of Queensland, Brisbane, Australia.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
van der Zee MD van der Zee Matthijs D MD Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
Cheesman R Cheesman Rosa R Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Mangino M Mangino Massimo M NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
Wang Y Wang Yunzhang Y Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Li S Li Shuai S Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Klaric L Klaric Lucija L MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Ratliff SM Ratliff Scott M SM Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Bielak LF Bielak Lawrence F LF Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Nygaard M Nygaard Marianne M Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Giannelis A Giannelis Alexandros A Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Willoughby EA Willoughby Emily A EA Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Reynolds CA Reynolds Chandra A CA Department of Psychology, University of California, Riverside, Riverside, CA, USA.
Balbona JV Balbona Jared V JV Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Andreassen OA Andreassen Ole A OA Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Ask H Ask Helga H Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
Baras A Baras Aris A Regeneron Genetics Center, Tarrytown, NY, USA.
Bauer CR Bauer Christopher R CR Biomedical and Translational Informatics, Geisinger Health, Danville, PA, USA.
Boomsma DI Boomsma Dorret I DI Amsterdam Public Health (APH) and Amsterdam Reproduction and Development (AR&D), Amsterdam, the Netherlands.
Campbell A Campbell Archie A Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Campbell H Campbell Harry H Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
Chen Z Chen Zhengming Z MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Christofidou P Christofidou Paraskevi P Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Corfield E Corfield Elizabeth E Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
Dahm CC Dahm Christina C CC Department of Public Health, Aarhus University, Aarhus, Denmark.
Dokuru DR Dokuru Deepika R DR Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Evans LM Evans Luke M LM Department of Ecology & Evolutionary Biology, University of Colorado at Boulder, Boulder, CO, USA.
de Geus EJC de Geus Eco J C EJC Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands.
Giddaluru S Giddaluru Sudheer S Norwegian Institute of Public Health, Oslo, Norway.
Gordon SD Gordon Scott D SD Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Harden KP Harden K Paige KP Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA.
Hill WD Hill W David WD Department of Psychology, University of Edinburgh, Edinburgh, UK.
Hughes A Hughes Amanda A Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Kerr SM Kerr Shona M SM MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Kim Y Kim Yongkang Y Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Kweon H Kweon Hyeokmoon H Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Latvala A Latvala Antti A Institute of Criminology and Legal Policy, Faculty of Social Sciences, University of Helsinki, Helsinki, Finland.
Lawlor DA Lawlor Deborah A DA Bristol NIHR Biomedical Research Centre, Bristol, UK.
Li L Li Liming L Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
Lin K Lin Kuang K Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Magnus P Magnus Per P Centre for Fertility and Health, Norwegian Institute of Public Health, Skøyen, Oslo, Norway.
Magnusson PKE Magnusson Patrik K E PKE Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mallard TT Mallard Travis T TT Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA.
Martikainen P Martikainen Pekka P Department of Public Health Sciences, Stockholm University, Stockholm, Sweden.
Mills MC Mills Melinda C MC Leverhulme Centre for Demographic Science, University of Oxford, Oxford, UK.
Njølstad PR Njølstad Pål Rasmus PR Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway.
Overton JD Overton John D JD Regeneron Genetics Center, Tarrytown, NY, USA.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Porteous DJ Porteous David J DJ Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Reid J Reid Jeffrey J Regeneron Genetics Center, Tarrytown, NY, USA.
Silventoinen K Silventoinen Karri K Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, Finland.
Southey MC Southey Melissa C MC Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Stoltenberg C Stoltenberg Camilla C Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Tucker-Drob EM Tucker-Drob Elliot M EM Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA.
Wright MJ Wright Margaret J MJ Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Social Science Genetic Association Consortium
Within Family Consortium
Hewitt JK Hewitt John K JK Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Keller MC Keller Matthew C MC Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Stallings MC Stallings Michael C MC Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, USA.
Lee JJ Lee James J JJ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Christensen K Christensen Kaare K Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Kardia SLR Kardia Sharon L R SLR Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Peyser PA Peyser Patricia A PA Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Smith JA Smith Jennifer A JA Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Wilson JF Wilson James F JF Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
Hopper JL Hopper John L JL Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
Hägg S Hägg Sara S Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Pingault JB Pingault Jean-Baptiste JB Department of Clinical, Educational and Health Psychology, University College London, London, UK.
Plomin R Plomin Robert R Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Havdahl A Havdahl Alexandra A Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
Bartels M Bartels Meike M Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Oskarsson S Oskarsson Sven S Department of Government, Uppsala University, Uppsala, Sweden.
Justice AE Justice Anne E AE Department of Population Health Sciences, Geisinger Health, Danville, PA, USA.
Millwood IY Millwood Iona Y IY MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Hveem K Hveem Kristian K HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
Naess Ø Naess Øyvind Ø Norwegian Institute of Public Health, Oslo, Norway.
Willer CJ Willer Cristen J CJ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Åsvold BO Åsvold Bjørn Olav BO Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Koellinger PD Koellinger Philipp D PD La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
Medland SE Medland Sarah E SE School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Walters RG Walters Robin G RG MRC Population Health Research Unit, University of Oxford, Oxford, UK.
Benjamin DJ Benjamin Daniel J DJ National Bureau of Economic Research, Cambridge, MA, USA.
Turley P Turley Patrick P Department of Economics, University of Southern California, Los Angeles, CA, USA.
Evans DM Evans David M DM Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Davey Smith G Davey Smith George G Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Hayward C Hayward Caroline C MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Brumpton B Brumpton Ben B HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway. ben.brumpton@ntnu.no.
Hemani G Hemani Gibran G Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. g.hemani@bristol.ac.uk.
Davies NM Davies Neil M NM K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. neil.davies@bristol.ac.uk.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Kweon Hyeokmoon H
Koellinger Philipp D PD
Benjamin Daniel J DJ
Turley Patrick P
Howe Laurence J LJ
Nivard Michel G MG
Morris Tim T TT
Hansen Ailin F AF
Rasheed Humaira H
Cho Yoonsu Y
Chittoor Geetha G
Ahlskog Rafael R
Lind Penelope A PA
Palviainen Teemu T
van der Zee Matthijs D MD
Cheesman Rosa R
Mangino Massimo M
Wang Yunzhang Y
Li Shuai S
Klaric Lucija L
Ratliff Scott M SM
Bielak Lawrence F LF
Nygaard Marianne M
Giannelis Alexandros A
Willoughby Emily A EA
Reynolds Chandra A CA
Balbona Jared V JV
Andreassen Ole A OA
Ask Helga H
Boomsma Dorret I DI
Campbell Archie A
Campbell Harry H
Chen Zhengming Z
Christofidou Paraskevi P
Corfield Elizabeth E
Dahm Christina C CC
Dokuru Deepika R DR
Evans Luke M LM
de Geus Eco J C EJC
Giddaluru Sudheer S
Gordon Scott D SD
Harden K Paige KP
Hill W David WD
Hughes Amanda A
Kerr Shona M SM
Kim Yongkang Y
Latvala Antti A
Lawlor Deborah A DA
Li Liming L
Lin Kuang K
Magnus Per P
Magnusson Patrik K E PKE
Mallard Travis T TT
Martikainen Pekka P
Mills Melinda C MC
Njølstad Pål Rasmus PR
Pedersen Nancy L NL
Porteous David J DJ
Silventoinen Karri K
Southey Melissa C MC
Stoltenberg Camilla C
Tucker-Drob Elliot M EM
Wright Margaret J MJ
Hewitt John K JK
Keller Matthew C MC
Stallings Michael C MC
Lee James J JJ
Christensen Kaare K
Kardia Sharon L R SLR
Peyser Patricia A PA
Smith Jennifer A JA
Wilson James F JF
Hopper John L JL
Hägg Sara S
Spector Tim D TD
Pingault Jean-Baptiste JB
Plomin Robert R
Havdahl Alexandra A
Bartels Meike M
Martin Nicholas G NG
Oskarsson Sven S
Justice Anne E AE
Millwood Iona Y IY
Hveem Kristian K
Naess Øyvind Ø
Willer Cristen J CJ
Åsvold Bjørn Olav BO
Kaprio Jaakko J
Medland Sarah E SE
Walters Robin G RG
Evans David M DM
Smith George Davey GD
Hayward Caroline C
Brumpton Ben B
Hemani Gibran G
Davies Neil M NM
JOURNAL
VOLUME: 54
ISSUE: 5
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2022
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MC_UU_00011 RCUK | Medical Research Council (MRC)
MC_UU_00011 RCUK | MRC | Medical Research Foundation
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Multifactorial Inheritance genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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