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

Tabea Schoeler; Doug Speed; Eleonora Porcu; Nicola Pirastu; Jean Baptiste Pingault; Zoltán Kutalik

doi:10.1038/s41562-023-01579-9

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

Tabea Schoeler^*, Doug Speed, Eleonora Porcu, Nicola Pirastu, Jean Baptiste Pingault, Zoltán Kutalik^*

^*Corresponding author af dette arbejde

Center for Kvantitativ Genetik og Genomforskning, Aarhus

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

132 Citationer (Scopus)

6 Downloads (Pure)

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 _effective = 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 ², 5%), we found substantial discrepancies for genetic correlations (maximum change in r _g, 0.31) and Mendelian randomization estimates (maximum change in β _STD, 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.

Originalsprog	Engelsk
Tidsskrift	Nature Human Behaviour
Vol/bind	7
Nummer	7
Sider (fra-til)	1216-1227
Antal sider	12
ISSN	2397-3374
DOI	https://doi.org/10.1038/s41562-023-01579-9
Status	Udgivet - jul. 2023

Adgang til dokumentet

10.1038/s41562-023-01579-9

s41562-023-01579-9Forlagets udgivne version, 1,95 MBLicens: CC BY

Citationsformater

@article{c11bf2763ea24f59ba7cd549fcbd1596,

title = "Participation bias in the UK Biobank distorts genetic associations and downstream analyses",

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 effective = 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 2, 5%), we found substantial discrepancies for genetic correlations (maximum change in r g, 0.31) and Mendelian randomization estimates (maximum change in β STD, 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 = "Biological Specimen Banks, Genome-Wide Association Study, Humans, Phenotype, United Kingdom/epidemiology",

author = "Tabea Schoeler and Doug Speed and Eleonora Porcu and Nicola Pirastu and Pingault, {Jean Baptiste} and Zolt{\'a}n Kutalik",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jul,

doi = "10.1038/s41562-023-01579-9",

language = "English",

volume = "7",

pages = "1216--1227",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

number = "7",

}

TY - JOUR

T1 - Participation bias in the UK Biobank distorts genetic associations and downstream analyses

AU - Schoeler, Tabea

AU - Speed, Doug

AU - Porcu, Eleonora

AU - Pirastu, Nicola

AU - Pingault, Jean Baptiste

AU - Kutalik, Zoltán

PY - 2023/7

Y1 - 2023/7

N2 - 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 effective = 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 2, 5%), we found substantial discrepancies for genetic correlations (maximum change in r g, 0.31) and Mendelian randomization estimates (maximum change in β STD, 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.

AB - 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 effective = 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 2, 5%), we found substantial discrepancies for genetic correlations (maximum change in r g, 0.31) and Mendelian randomization estimates (maximum change in β STD, 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.

KW - Biological Specimen Banks

KW - Genome-Wide Association Study

KW - Humans

KW - Phenotype

KW - United Kingdom/epidemiology

U2 - 10.1038/s41562-023-01579-9

DO - 10.1038/s41562-023-01579-9

M3 - Journal article

C2 - 37106081

AN - SCOPUS:85153782421

SN - 2397-3374

VL - 7

SP - 1216

EP - 1227

JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 7

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater