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Multiple measures of depression to enhance validity of Major Depressive Disorder in the UK Biobank

By Kylie Patricia Glanville, Jonathan RI Coleman, David M Howard, Oliver Pain, Ken B Hanscombe, Bradley Scott Jermy, Ryan Arathimos, Christopher Huebel, Gerome Breen, Paul F O'Reilly, Cathryn Lewis

Posted 22 Sep 2020
medRxiv DOI: 10.1101/2020.09.18.20196451

Background: The UK Biobank (UKB) contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders. Aims: To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of Major Depressive Disorder. Methods: In participants who did not complete the MHQ (n = 325k), we calculated the number of other depression measures endorsed, e.g. from hospital episode statistics and interview data. We compared cases defined this way to CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, SNP-based heritability, and genetic correlations with summary statistics from the Psychiatric Genomics Consortium Major Depressive Disorder (PGC MDD) GWAS. Results: The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in cases who endorsed only one measure of depression, to 21% in cases who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UKB and PGC MDD exceeded 0.7, but there was variability between pairwise comparisons. Conclusions: Multiple measures of depression can serve as a reliable approximation for case-status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UKB data.

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