Abstract
The UK Biobank 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. To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD). In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study. The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those 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 UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons. 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 UK Biobank data.
Highlights
The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression
We compared cases defined this way with Composite International Diagnostic Interview (CIDI)-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium major depressive disorder (MDD) genome-wide association study
SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression
Summary
The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. The UK Biobank contains extensive data items that are relevant to psychiatric phenotyping, ranging from electronic health records to self-reported health data, and questionnaires that rely on retrospective recall of symptoms.[2] The extent to which each source of information accurately classifies cases and controls for a given trait influences any study that is performed, by affecting power and interpretation of effect sizes.[3] In genetic studies of polygenic traits, large sample sizes are a prerequisite for performing a genome-wide association study (GWAS), but investigators must balance phenotypic rigour against sample size, and missing data, where individuals do not meet criteria for either ‘cases’ or ‘controls’ These issues are salient in disorders such as MDD, which encompass a spectrum of symptom severity and within-disorder phenotypic heterogeneity.[4]
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