Evidence map›Paper›PMID 41282763›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Family-GWAS reveals effects of environment and mating on genetic associations.

Tammy Tan, Hariharan Jayashankar, Junming Guan, Seyed Moeen Nehzati, Mahdi Mir, Michael Bennett, Esben Agerbo, Rafael Ahlskog, Ville Pinto de Andrade Anapaz, Bjørn Olav Åsvold and 66 more

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Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

76 authors.

Tammy TanNational Bureau of Economic Research, Cambridge, MA, USA.
Hariharan JayashankarUCLA Anderson School of Management, Los Angeles, CA, USA.
Junming GuanUCLA Anderson School of Management, Los Angeles, CA, USA.
Seyed Moeen NehzatiUCLA Anderson School of Management, Los Angeles, CA, USA.
Mahdi MirUCLA Anderson School of Management, Los Angeles, CA, USA.
Michael BennettNational Bureau of Economic Research, Cambridge, MA, USA.
Esben AgerboNational Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
Rafael AhlskogDepartment of Government, Uppsala university.ORCID 0000-0002-4327-447X
Ville Pinto de Andrade AnapazInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Bjørn Olav ÅsvoldHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.ORCID 0000-0003-3837-2101
Stefania BenonisdottirBig Data Institute, Li Ka Shing Centre for Health Information Discovery, University of Oxford, Oxford OX3 7LF, UK.
Laxmi BhattaHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
Dorret I BoomsmaDepartment of Complex Traits Genetics CNCR, Vrije Universiteit Amsterdam, De Boelelaan 1105 1081 HV Amsterdam, The Netherlands.ORCID 0000-0002-7099-7972
Ben BrumptonHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.ORCID 0000-0002-3058-1059
Archie CampbellCentre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Christopher F ChabrisDepartment of Bioethics & Decision Sciences, Geisinger Health System, 100 North Academy Avenue, Danville, PA 17822 USA.
Rosa CheesmanPROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
Zhengming ChenNuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.
China Kadoorie Biobank Collaborative Group
Eco de GeusDepartment of Biological Psychology, Vrije Universiteit Amsterdam, De Boelelaan 1105 1081 HV Amsterdam, The Netherlands.
Erik A EhliAvera Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, SD 57105, USA.
Abdelrahman G ElnahasInstitute of Genomics, University of Tartu, Tartu, Estonia.
Estonian Biobank Research Team
Finngen
Andrea GannaInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Alexandros GiannelisDepartment of Psychology, University of Minnesota Twin Cities, 75 East River Road, Minneapolis, MN 55455, USA.
Liisa HakasteInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Ailin Falkmo HansenHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
Alexandra HavdahlPROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Jouke-Jan HottengaAvera Genetics, Avera McKennan Hospital & University Health Center, Sioux Falls, SD 57105, USA.
Mikkel Aagaard HoumarkDepartment of Economics and Business Economics and TrygFonden's Centre for Child Research, Aarhus University, Fuglesangs Allé 4, 8210 Aarhus V, Denmark.
Kristian HveemHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
Jaakko KaprioInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.ORCID 0000-0002-3716-245
Arnulf LanghammerHUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, 7600, Norway.
Antti LatvalaInstitute of Criminology and Legal Policy, University of Helsinki.
James J LeeDepartment of Psychology, University of Minnesota Twin Cities, 75 East River Road, Minneapolis, MN 55455, USA.
Mikko LehtovirtaInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Liming LiDepartment of Epidemiology & Biostatistics, School of Public Health, Peking University, Xueyuan Road, Haidian District, 100191, Beijing, China.
LifeLines Cohort Study
Kuang LinNuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.
Richard Karlsson LinnérDepartment of Economics, Leiden Law School, Leiden University, Steenschuur 25, 2311 ES Leiden, the Netherlands.ORCID 0000-0001-7839-2858
Stefano LombardiInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Nicholas G MartinMental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Matt McGueDepartment of Psychology, University of Minnesota Twin Cities, 75 East River Road, Minneapolis, MN 55455, USA.
Sarah E MedlandMental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Andres MetspaluInstitute of Genomics, University of Tartu, Tartu, Estonia.
Brittany L MitchellMental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Guiyan NiInstitute for Molecular Bioscience, University of Queensland, Australia.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Matthew T OetjensAutism and Developmental Medicine Institute, Geisinger Health System, 120 Hamm Drive, Lewisburg, PA 17837, USA.
Sven OskarssonDepartment of Government, Uppsala university.
Teemu PalviainenInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Rashmi B PrasadInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.ORCID 0000-0002-4400-6741
Anu ReigoInstitute of Genomics, University of Tartu, Tartu, Estonia.
Kadri ReisInstitute of Genomics, University of Tartu, Tartu, Estonia.
Julia SidorenkoInstitute for Molecular Bioscience, University of Queensland, Australia.
Karri SilventoinenHelsinki Institute for Demography and Population Health, University of Helsinki, Helsinki, Finland.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Tiinamaija TuomiInstitute for Molecular Medicine Finland FIMM, HILife, University of Helsinki, Helsinki, FIN-00140 Finland.
Bjarni J VilhjálmssonNational Centre for Register-based Research, Aarhus University.
Robin G WaltersNuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.ORCID 0000-0002-9179-0321
Emily A WilloughbyDepartment of Psychology, University of Minnesota Twin Cities, 75 East River Road, Minneapolis, MN 55455, USA.
Bendik S WinsvoldHUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, 7030, Norway.
Eivind YstromPROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
Jonathan FlintUCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA, USA.
Loic YengoInstitute for Molecular Bioscience, University of Queensland, Australia.
Peter M VisscherNuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford OX3 7LF, UK.
Augustine KongLeverhulme Centre for Demographic Science, Nuffield Department of Population Health, University of Oxford and Nuffield College, UK.
Elliot M Tucker-DrobDepartment of Psychology, The University of Texas at Austin, 108 E. Dean Keeton Stop A8000, Austin, TX 78712, USA.
Richard BorderDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 885 Tiverton Dr., Los Angeles, CA 90095.ORCID 0000-0002-6293-2968
David CesariniNational Bureau of Economic Research, Cambridge, MA, USA.
Patrick TurleyDepartment of Economics, University of Southern California, Los Angeles, CA, USA.
Aysu OkbayDepartment of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Daniel J BenjaminNational Bureau of Economic Research, Cambridge, MA, USA.
Alexander Strudwick YoungUCLA Anderson School of Management, Los Angeles, CA, USA.ORCID 0000-0001-9930-989X

Funding

Dissecting the Multivariate Genetic Architecture of Psychiatric DiseasesR01MH120219 · NIMH · UNIVERSITY OF TEXAS AT AUSTIN · PI NIVARD, MICHEL GUILLAUME, TUCKER-DROB, ELLIOT MAX · 2020 to 2024
$3.3M
Mendelian imputation for family-based GWAS and association-by-proxy in diverse ancestriesR01AG083379 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alexander Thomas Ian Strudwick Young · 2023 to 2026
$3.1M
Genome-Wide Analyses of Health and Well-Being PhenotypesR01AG042568 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BENJAMIN, DANIEL J · 2015 to 2021
$2.8M
Infrastructure and Core Activities of the Social Science Genetic Association ConsortiumR24AG065184 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BENJAMIN, DANIEL J · 2019 to 2023
$1.8M
Genome-wide analysis of late-onset Alzheimer's disease using intergenerational, multi-trait, and cross-ancestry dataR00AG062787 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TURLEY, PATRICK ANSEL · 2021 to 2023
$747k
NIA NIH HHS R00 AG062787NIA NIH HHS R01 AG042568NIA NIH HHS R01 AG083379NIA NIH HHS R24 AG065184NIMH NIH HHS R01 MH120219
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) have discovered thousands of replicable genetic associations, guiding drug target discovery and powering genetic prediction of human phenotypes and diseases. However, genetic associations can be affected by gene-environment correlations and non-random mating, which can lead to biased inferences in downstream analyses. Family-based GWAS (FGWAS) uses the natural experiment of random assignment of genotype within families to separate out the contribution of direct genetic effects (DGEs) - causal effects of alleles in an individual on an individual - from other factors contributing to genetic associations. Here, we report results from an FGWAS meta-analysis of 34 phenotypes from 17 cohorts. We found evidence that factors uncorrelated with DGEs make substantial contributions to genetic associations for 27 phenotypes, with population stratification confounding - a form of gene-environment correlation - likely the major cause. By estimating SNP heritability and genetic correlations using DGEs, we found evidence that assortative mating has led to overestimation of SNP heritability for 5 phenotypes and overestimation of the degree of shared genetic effects (pleiotropy) between 22 pairs of phenotypes. Polygenic predictors constructed from DGEs are particularly useful for studying natural selection, assortative mating, and indirect genetic effects (effects of relatives' genes mediated through the family environment). We validate our meta-analysis results by predicting phenotypes in hold-out samples using polygenic predictors constructed from DGEs, achieving statistically significant out-of-sample prediction for 24 phenotypes with little attenuation of predictive power within-families. We provide FGWAS summary statistics for 34 phenotypes that can be used for downstream analyses. Our study provides both a template for performing FGWAS and an argument for its value for debiasing inferences and understanding the impact of environment and mating patterns.

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PMID41282763
PMCPMC12633112

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