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

Cai, Na, Revez, Joana A, Adams, Mark J, Andlauer, Till FM, Breen, Gerome, Byrne, Enda M, Clarke, Toni-Kim, Forstner, Andreas J, Grabe, Hans J, Hamilton, Steven P
et al (show 22 more authors) (2020) Minimal phenotyping yields genome-wide association signals of low specificity for major depression. NATURE GENETICS, 52 (4). 437-+.

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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.

Item Type: Article
Uncontrolled Keywords: MDD Working Group of the Psychiatric Genomics Consortium, Humans, Genetic Predisposition to Disease, Risk Factors, Sensitivity and Specificity, Bipolar Disorder, Depressive Disorder, Major, Genotype, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Genome-Wide Association Study
Depositing User: Symplectic Admin
Date Deposited: 13 May 2020 09:32
Last Modified: 18 Jan 2023 23:52
DOI: 10.1038/s41588-020-0594-5
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