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

Abstract

BackgroundThe 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. AimsTo investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of Major Depressive Disorder. MethodsIn 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 the strength of the genetic contribution in cases defined this way, to CIDI-defined cases. We compared 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. ResultsThe strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% with one measure of depression to 21% with four or five. 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. ConclusionsMultiple measures of depression can serve as a reliable approximation for case-status where the CIDI measure is not available, with the implication that sample size can be optimised using the full suite of UKB data.