Participation bias in the UK Biobank distorts genetic associations and downstream analyses.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_01935437E212
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Participation bias in the UK Biobank distorts genetic associations and downstream analyses.
Journal
Nature human behaviour
Author(s)
Schoeler T., Speed D., Porcu E., Pirastu N., Pingault J.B., Kutalik Z.
ISSN
2397-3374 (Electronic)
ISSN-L
2397-3374
Publication state
Published
Issued date
07/2023
Peer-reviewed
Oui
Volume
7
Number
7
Pages
1216-1227
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
While volunteer-based studies such as the UK Biobank have become the cornerstone of genetic epidemiology, the participating individuals are rarely representative of their target population. To evaluate the impact of selective participation, here we derived UK Biobank participation probabilities on the basis of 14 variables harmonized across the UK Biobank and a representative sample. We then conducted weighted genome-wide association analyses on 19 traits. Comparing the output from weighted genome-wide association analyses (n <sub>effective</sub> = 94,643 to 102,215) with that from standard genome-wide association analyses (n = 263,464 to 283,749), we found that increasing representativeness led to changes in SNP effect sizes and identified novel SNP associations for 12 traits. While heritability estimates were less impacted by weighting (maximum change in h <sup>2</sup> , 5%), we found substantial discrepancies for genetic correlations (maximum change in r <sub>g</sub> , 0.31) and Mendelian randomization estimates (maximum change in β <sub>STD</sub> , 0.15) for socio-behavioural traits. We urge the field to increase representativeness in biobank samples, especially when studying genetic correlates of behaviour, lifestyles and social outcomes.
Keywords
Humans, Genome-Wide Association Study, Biological Specimen Banks, Phenotype, United Kingdom/epidemiology
Pubmed
Web of science
Open Access
Yes
Create date
02/05/2023 9:59
Last modification date
23/01/2024 8:20
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