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Minimal phenotyping yields genome-wide association signals of low specificity for major depression

Cai, N; Revez, JA; Adams, MJ; Andlauer, TFM; Breen, G; Byrne, EM; Clarke, T-K; ... Flint, J; + view all (2020) Minimal phenotyping yields genome-wide association signals of low specificity for major depression. Nature Genetics , 52 pp. 437-447. 10.1038/s41588-020-0594-5. Green open access

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Abstract

Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.

Type: Article
Title: Minimal phenotyping yields genome-wide association signals of low specificity for major depression
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-020-0594-5
Publisher version: https://doi.org/10.1038/s41588-020-0594-5
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Computational biology and bioinformatics, Diseases, Genetics, Genome-wide association studies, Medical research
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10096565
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