ArticleNature communications2020
Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses.
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Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers, 5 of them syntheses that pooled it.
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244citing papers in PubMed, 5 pooled it
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Who cites it
244 citing papers in PubMed, 5 syntheses or guidelines pooled it, 409 citations in OpenAlex.
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- Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review.International journal of epidemiology · 2023Pooled it
- Cross-fitted instrument: A blueprint for one-sample Mendelian randomization.PLoS computational biology · 2022Pooled it
- Multivariate GWAS framework for family trios with parental phenotypes to control dynastic effects.BMC bioinformatics · 2026Article
- Childhood Correlates of Genetic Propensity to Personality Traits.medRxiv : the preprint server for health sciences · 2026Article
- Association Between Socioeconomic Status and Atrial Fibrillation: A Two-Sample Mendelian Randomization Study.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2026Article
- Beyond years of schooling: Genetic associations across educational milestones in two Norwegian cohorts.PLoS genetics · 2026Article
- Investigating relationships between loneliness, social isolation and health.Nature communications · 2026Article
- Comparison of methods for assessing effects of risk factors on disease progression in Mendelian randomization under index event bias.American journal of human genetics · 2026Article
- Causal inference in psychiatric research: how to critically evaluate and interpret mendelian randomization studies.Molecular psychiatry · 2026Review
- The influence of unhealthy lifestyle on semen quality: results from a cross-sectional study and Mendelian randomization analysis.Annals of medicine and surgery (2012) · 2026Article
- Evaluating confounding in rare variant genome wide association studies.Nature communications · 2026Article
- Genome-wide association study of positive and negative affect reveals shared genetic architecture and a potential causal relationship with cognition.Scientific reports · 2026Article
- The tissue-specific effects of glucose-lowering drug targets on aging mediated through DNA methylation: a multi-omics genetic study.BMC medicine · 2026Article
- Genomic-Relatedness Matching Expands Population Coverage, Improves Power, and Reduces Bias in Genetic Association Analyses.medRxiv : the preprint server for health sciences · 2026Article
- Estimating uncertainty in family-based GWAS.bioRxiv : the preprint server for biology · 2026Article
- Adolescent wellbeing is associated with positive outcomes in early adulthood in a sibling comparison study.Nature communications · 2026Article
- Challenges and future directions for Mendelian randomization.Nature genetics · 2026Review
184 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 15 institutions in 8 countries.
Ben BrumptonK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. ben.brumpton@ntnu.no.ORCID http://orcid.org/0000-0002-3058-1059
Eleanor SandersonMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0001-5188-5775
Karl Heilbron23andMe, Inc., 223 N Mathilda Avenue, Sunnyvale, CA, 94086, USA.
Fernando Pires HartwigMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0003-3729-0710
Sean HarrisonMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0002-7966-0700
Gunnhild Åberge VieK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.ORCID http://orcid.org/0000-0003-1552-5291
Yoonsu ChoMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0001-6118-6652
Laura D HoweMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.
Amanda HughesMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.
Dorret I BoomsmaNetherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Alexandra HavdahlMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0002-9268-0423
John HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie Street, Carlton, VIC, 3053, Australia.
Michael NealeVirginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.ORCID http://orcid.org/0000-0003-4887-659X
Michel G NivardNetherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0003-2015-1888
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Chandra A ReynoldsDepartment of Psychology, University of California Riverside, Riverside, CA, USA.
Elliot M Tucker-DrobDepartment of Psychology and Population Research Center, University of Texas at Austin, 108 E. Dean Keeton Stop A8000,, Austin, TX, 78712, USA.
Andrew GrotzingerDepartment of Psychology and Population Research Center, University of Texas at Austin, 108 E. Dean Keeton Stop A8000,, Austin, TX, 78712, USA.ORCID http://orcid.org/0000-0001-7852-9244
Laurence HoweMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.
Tim MorrisMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0001-8178-6815
Shuai LiCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie Street, Carlton, VIC, 3053, Australia.
Within-family Consortium
23andMe Research Team
Adam Auton23andMe, Inc., 223 N Mathilda Avenue, Sunnyvale, CA, 94086, USA.
Frank WindmeijerMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.
Wei-Min ChenCenter for public health genomics, Department of public health sciences, University of Virginia, Charlottesville, VA, USA.
Johan Håkon BjørngaardK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Cristen WillerDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5645-4966
David M EvansMedical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0003-0663-4621
Jaakko KaprioDepartment of Public Health, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-3716-2455
George Davey Smith *Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0002-1407-8314
Bjørn Olav Åsvold *K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Gibran Hemani *Medical Research Council Integrative Epidemiology Unit, University of Bristol, BS8 2BN, Bristol, UK.ORCID http://orcid.org/0000-0003-0920-1055
Neil M Davies *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.ORCID http://orcid.org/0000-0002-2460-0508
University of Bristol · GBNorwegian University of Science and Technology · NO23andMe (United States) · USThe University of Melbourne · AUUniversity of Helsinki · FINorwegian Institute of Public Health · NOThe University of Texas at Austin · USUniversity of California, Riverside · USKarolinska Institutet · SENord University · NOThe University of Queensland · AUUniversidade Federal de Pelotas · BRVirginia Commonwealth University · USVrije Universiteit Amsterdam · NLUniversity of Cambridge · GB
Funding
Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife2)R01AG046938 · NIA · UNIVERSITY OF COLORADO · PI REYNOLDS, CHANDRA A, WADSWORTH, SALLY J · 2015 to 2024
$18.5MThe VETSA longitudinal twin study of cognition and agingR01AG018386 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KREMEN, WILLIAM S. · 2002 to 2012
$9.7MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MScientific & Technical CoreP2CHD042849 · NICHD · UNIVERSITY OF TEXAS AT AUSTIN · PI MARK D. HAYWARD · 2017 to 2026
$5.2MSex differences in the relationship between APOE and AD: Role of sexual differentiationRF1AG058068 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GATZ, MARGARET, LADU, MARY JO · 2017 to 2017
$3.8MClarifying risk and protective factors for dementia with the Interplay of Genes and Environment in Multiple Studies (IGEMS) consortiumR01AG060470 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GATZ, MARGARET, PEDERSEN, NANCY L · 2018 to 2022
$3.6MCortisol, Socioeconomic Status, and Genetic Influences on Cognitive DevelopmentR01HD083613 · NICHD · UNIVERSITY OF TEXAS AT AUSTIN · PI TUCKER-DROB, ELLIOT MAX · 2016 to 2020
$3.0MSES health gradients in late life: testing models of gene-environment interplay in an international twin consortiumR01AG059329 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FINCH, BRIAN K., GATZ, MARGARET · 2018 to 2022
$2.9MEvaluating Longitudinal Changes in the Human Structural Connectome in Relation to Cognitive AgingR01AG054628 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI TUCKER-DROB, ELLIOT MAX · 2017 to 2021
$2.7MMedical Research Council MC_PC_13049Medical Research Council MC_PC_14135Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_U137686851Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/2Medical Research Council MC_UU_00017/1Medical Research Council MC_UU_12013/4Medical Research Council MC_UU_12026/2Medical Research Council MR/M020894/1NHLBI NIH HHS R01 HL105756NIA NIH HHS R01 AG018386NIA NIH HHS R01 AG046938NIA NIH HHS R01 AG054628NIA NIH HHS R01 AG059329NIA NIH HHS R01 AG060470NIA NIH HHS RF1 AG058068NICHD NIH HHS P2C HD042849NICHD NIH HHS R01 HD083613Wellcome TrustWellcome Trust 208806/Z/17/ZWellcome Trust WT104150
Abstract
Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.
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Body Mass IndexEpidemiologyFemaleHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk Factors
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