Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
05
03
2021
accepted:
25
03
2022
pubmed:
10
5
2022
medline:
20
5
2022
entrez:
9
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35534559
doi: 10.1038/s41588-022-01062-7
pii: 10.1038/s41588-022-01062-7
pmc: PMC9110300
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
581-592Subventions
Organisme : Medical Research Council
ID : MC_UU_00011/6
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL109946
Pays : United States
Organisme : Medical Research Council
ID : MR/T030852/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208806/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG042568
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R24 AG065184
Pays : United States
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R026408/1
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : P2C HD042849
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG042568
Pays : United States
Investigateurs
Hyeokmoon Kweon
(H)
Philipp D Koellinger
(PD)
Daniel J Benjamin
(DJ)
Patrick Turley
(P)
Laurence J Howe
(LJ)
Michel G Nivard
(MG)
Tim T Morris
(TT)
Ailin F Hansen
(AF)
Humaira Rasheed
(H)
Yoonsu Cho
(Y)
Geetha Chittoor
(G)
Rafael Ahlskog
(R)
Penelope A Lind
(PA)
Teemu Palviainen
(T)
Matthijs D van der Zee
(MD)
Rosa Cheesman
(R)
Massimo Mangino
(M)
Yunzhang Wang
(Y)
Shuai Li
(S)
Lucija Klaric
(L)
Scott M Ratliff
(SM)
Lawrence F Bielak
(LF)
Marianne Nygaard
(M)
Alexandros Giannelis
(A)
Emily A Willoughby
(EA)
Chandra A Reynolds
(CA)
Jared V Balbona
(JV)
Ole A Andreassen
(OA)
Helga Ask
(H)
Dorret I Boomsma
(DI)
Archie Campbell
(A)
Harry Campbell
(H)
Zhengming Chen
(Z)
Paraskevi Christofidou
(P)
Elizabeth Corfield
(E)
Christina C Dahm
(CC)
Deepika R Dokuru
(DR)
Luke M Evans
(LM)
Eco J C de Geus
(EJC)
Sudheer Giddaluru
(S)
Scott D Gordon
(SD)
K Paige Harden
(KP)
W David Hill
(WD)
Amanda Hughes
(A)
Shona M Kerr
(SM)
Yongkang Kim
(Y)
Antti Latvala
(A)
Deborah A Lawlor
(DA)
Liming Li
(L)
Kuang Lin
(K)
Per Magnus
(P)
Patrik K E Magnusson
(PKE)
Travis T Mallard
(TT)
Pekka Martikainen
(P)
Melinda C Mills
(MC)
Pål Rasmus Njølstad
(PR)
Nancy L Pedersen
(NL)
David J Porteous
(DJ)
Karri Silventoinen
(K)
Melissa C Southey
(MC)
Camilla Stoltenberg
(C)
Elliot M Tucker-Drob
(EM)
Margaret J Wright
(MJ)
John K Hewitt
(JK)
Matthew C Keller
(MC)
Michael C Stallings
(MC)
James J Lee
(JJ)
Kaare Christensen
(K)
Sharon L R Kardia
(SLR)
Patricia A Peyser
(PA)
Jennifer A Smith
(JA)
James F Wilson
(JF)
John L Hopper
(JL)
Sara Hägg
(S)
Tim D Spector
(TD)
Jean-Baptiste Pingault
(JB)
Robert Plomin
(R)
Alexandra Havdahl
(A)
Meike Bartels
(M)
Nicholas G Martin
(NG)
Sven Oskarsson
(S)
Anne E Justice
(AE)
Iona Y Millwood
(IY)
Kristian Hveem
(K)
Øyvind Naess
(Ø)
Cristen J Willer
(CJ)
Bjørn Olav Åsvold
(BO)
Jaakko Kaprio
(J)
Sarah E Medland
(SE)
Robin G Walters
(RG)
David M Evans
(DM)
George Davey Smith
(GD)
Caroline Hayward
(C)
Ben Brumpton
(B)
Gibran Hemani
(G)
Neil M Davies
(NM)
Informations de copyright
© 2022. The Author(s).
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