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Genetic predictors of participation in optional components of UK Biobank

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Tyrrell, Jessica, Zheng, Jie, Beaumont, Robin, Hinton, Kathryn, Richardson, Tom G., Wood, Andrew R., Davey Smith, George, Frayling, Timothy M., Tilling, Kate·2021·Nature Communications

DOI 10.1038/s41467-021-21073-yPMC PMC7873270

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Abstract

Large studies such as UK Biobank are increasingly used for GWAS and Mendelian randomization (MR) studies. However, selection into and dropout from studies may bias genetic and phenotypic associations. We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants. We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies. 32 variants were associated with participation in one of the optional components ( P < 6 × 10 −9 ), including loci with links to intelligence and Alzheimer’s disease. Genetic correlations demonstrated that participation bias was common across studies. MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation. Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses.

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Fig. 1 Plots of the Mendelian Randomisation results. Dot plots representing the inverse-variance weighted results from two-sample MR analyses for (A) educational, (B) anthropometric, (C) behavioural and (D) neurological and psychological traits. Error bars represent the 95% confidence intervals of the IVW estimate.CC BY · PubMed Central

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Authors: Tyrrell, J., Zheng, J., Beaumont, R., Hinton, K., Richardson, T. G., Wood, A. R., Davey Smith, G., Frayling, T. M., & Tilling, K.
Affiliations: University of Exeter (GB)
University of Bristol (GB)
Corresponding author: Tyrrell, Jessica
Tilling, Kate
ORCID: Tyrrell, Jessica
Zheng, Jie
Beaumont, Robin
Richardson, Tom G.
Wood, Andrew R.
Davey Smith, George
Frayling, Timothy M.
Tilling, Kate
Venue: Nature Communications
Publisher: Springer Science and Business Media LLC
Published: 2021-02-09
Volume: 12
Issue: 1
Pages: 886-886
ISSN: 2041-1723 (ISSN-L)
DOI: 10.1038/s41467-021-21073-y
PMC: PMC7873270
OpenAlex: W3119247746
Cited by: 162
References: 43
Citations by year: 2026: 14 · 2025: 16 · 2024: 30 · 2023: 36 · 2022: 43 · 2021: 15
FWCI: 17.65
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Nature Communications (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Explore Bristol Research (acceptedVersion, cc-by)
Bristol Research (University of Bristol) (acceptedVersion, cc-by)
RePEc: Research Papers in Economics (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
Funders: Academy of Medical Sciences (SBF004\1079)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords: research participation, UK Biobank, genetic correlation, Mendelian randomization, educational attainment, age at menarche, height, adiposity, dyslipidemia, neuroticism, Alzheimer's disease, schizophrenia
MeSH terms: Community Participation, Female, United Kingdom, Humans, Male, Middle Aged, Risk Factors, Genetic Variation, Selection Bias, Biological Specimen Banks, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetic Loci, Mendelian Randomization Analysis

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Genetic predictors of participation in optional components of UK Biobank

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