A Re-evaluation of Candidate Gene Studies for Well-Being in Light of Genome-Wide Evidence

M.P. van de Weijer, D.H.M. Pelt, L.P. de Vries, B.M.L. Baselmans, M. Bartels

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    Abstract

    Ever since twin-family studies found that a substantial amount (± 40%) of the variation in well-being can be explained by genetic variation, several candidate genes have been proposed explaining this variation. However, these candidate gene and candidate gene-by-environment interaction studies have been surrounded by controversy regarding the validity and replication of their results. In the present study, we review the existing candidate gene literature for well-being. First, we perform a systematic literature search that results in the inclusion of 41 studies. After describing the results of the included studies, we evaluated the included candidate polymorphisms by (1) looking up the results for the studied candidate SNPs in a large well-being genome-wide association study, (2) performing association analyses in UK biobank (UKB) data for the candidate variable number tandem repeats (VNTR) and the APOE ε4 allele, and (3) studying possible candidate interactions with positive and negative environmental moderators using UKB data. We find no support for any of the candidate genes or candidate gene-environment interactions for well-being, with the exception of two SNPs that were chosen based on genome-wide evidence. While the generalizability of our findings is limited by our phenotype and environment definitions, we strongly advise well-being researchers to abandon the candidate gene approach in the field of well-being and move toward genome-wide approaches.
    Original languageEnglish
    Pages (from-to)3031–3053
    Number of pages23
    JournalJournal of Happiness Studies
    Volume23
    Issue number6
    Early online date17 May 2022
    DOIs
    Publication statusPublished - Aug 2022

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