Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Howe, Laurence J.; Nivard, Michel G.; Morris, Tim; Hansen, Ailin Falkmo; Rasheed, Humaira; Cho, Yoonsu; Chittoor, Geetha; Ahlskog, Rafael; Lind, Penelope A.; Palviainen, Teemu; Zee, Matthijs D. van der; 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 C.; Dahm, Christina C.; Dokuru, Deepika; Evans, Luke M.; Geus, Eco J. C. de; Giddaluru, Sudheer; Gordon, Scott D.; Harden, K. Paige; Hill, W. David; Hughes, Amanda; Kerr, Shona M.; Kim, Yongkang; Kweon, Hyeokmoon; Latvala, Antti; Lawlor, Debbie A.; Li, Liming; Lin, Kuang; Magnus, Per; Magnusson, Patrik K. E.; Mallard, Travis T.; Martikainen, Pekka; Mills, Melinda C.; Njølstad, Pål R.; Overton, John D.; Pedersen, Nancy L.; Porteous, David J.; Reid, Jeffrey G.; Silventoinen, Karri; Southey, Melissa C.; Stoltenberg, Camilla; Tucker–Drob, Elliot M.; Wright, Margaret J.; Kweon, Hyeokmoon; Koellinger, Philipp; Benjamin, Daniel J.; Turley, Patrick; Howe, Laurence J.; Nivard, Michel G.; Morris, Tim; Hansen, Ailin Falkmo; Rasheed, Humaira; Cho, Yoonsu; Chittoor, Geetha; Ahlskog, Rafael; Lind, Penelope A.; Palviainen, Teemu; Zee, Matthijs D. van der; 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; Boomsma, Dorret I.; Campbell, Archie; Campbell, Harry; Chen, Zhengming; Christofidou, Paraskevi; Corfield, Elizabeth C.; Dahm, Christina C.; Dokuru, Deepika; Evans, Luke M.; Geus, Eco J. C. de; Giddaluru, Sudheer; Gordon, Scott D.; Harden, K. Paige; Hill, W. David; Hughes, Amanda; Kerr, Shona M.; Kim, Yongkang; Latvala, Antti; Lawlor, Deborah A.; Li, Liming; Lin, Kuang; Magnus, Per; Magnusson, Patrik K. E.; Mallard, Travis T.; Martikainen, Pekka; Mills, Melinda C.; Njølstad, Pål R.; Pedersen, Nancy L.; Porteous, David J.; Silventoinen, Karri; Southey, Melissa C.; Stoltenberg, Camilla; Tucker–Drob, Elliot M.; Wright, Margaret J.; Hewitt, John K.; Keller, Matthew C.; Stallings, Michael C.; Lee, James J.; Christensen, Kaare; Kardia, Sharon L. R.; Peyser, Patricia A.; Smith, Jennifer A.; Wilson, James F.; Hopper, John L.; Hägg, Sara; Spector, Tim D.; Pingault, Jean‐Baptiste; Plomin, Robert; Havdahl, Alexandra; Bartels, Meike; Martin, Nicholas G.; Oskarsson, Sven; Justice, Anne E.; Millwood, Iona Y.; Hveem, Kristian; Næss, Øyvind; Willer, Cristen J.; Åsvold, Bjørn Olav; Kaprio, Jaakko; Medland, Sarah E.; Walters, Robin; Evans, David M.; Smith, George Davey; Hayward, Caroline; Brumpton, Ben; Hemani, Gibran; Davies, Neil M; Hewitt, John K.; Keller, Matthew C.; Stallings, Michael C.; Lee, James J.; Christensen, Kaare; Kardia, Sharon L. R.; Peyser, Patricia A.; Smith, Jennifer A.; Wilson, James F.; Hopper, John L.; Hägg, Sara; Spector, Tim D.; Pingault, Jean‐Baptiste; Plomin, Robert; Havdahl, Alexandra; Bartels, Meike; Martin, Nicholas G.; Oskarsson, Sven; Justice, Anne E.; Millwood, Iona Y.; Hveem, Kristian; Næss, Øyvind; Willer, Cristen J.; Åsvold, Bjørn Olav; Koellinger, Philipp; Kaprio, Jaakko; Medland, Sarah E.; Walters, Robin; Benjamin, Daniel J.; Turley, Patrick; Evans, David M.; Smith, George Davey; Hayward, Caroline; Brumpton, Ben; Hemani, Gibran; Davies, Neil M

doi:10.1038/s41588-022-01062-7

articleNature GeneticsMay 1, 2022HYBRID OA

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

LJLaurence J. HoweMGMichel G. Nivard TMTim Morris AFAilin Falkmo HansenHRHumaira Rasheed

Bristol City Council · At Bristol · +54 more institutions

PubMed

Indexed incrossrefdatacitepubmed

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…

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Authors

196

LJ
Laurence J. HoweCorresponding
Bristol City Council, At Bristol, University of Bristol, Medical Research Council
MG
Michel G. Nivard
Vrije Universiteit Amsterdam
TM
Tim Morris
University of Bristol, Medical Research Council
AF
Ailin Falkmo Hansen
Norwegian University of Science and Technology
HR
Humaira Rasheed
Norwegian University of Science and Technology, University of Bristol, Medical Research Council

Topics & keywords

Topics

Keywords

Genome-wide association study
Biology
Assortative mating
Heritability
Population stratification
Genetic association
Mendelian randomization
Genetics

UN Sustainable Development Goals

Good health and well-being

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