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

Abstract

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 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. Results: The 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. Conclusions: Multiple 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.

Comparison of algorithm-based versus single-item diagnostic measures of anxiety and depression disorders in the GLAD and COPING cohorts

“…Our results suggest that single-item diagnoses may be sufficient for discovery of shared genetic effects, but investigation of disorder-specific factors or outcomes would require an algorithm-based or other strictly-defined measure. In designing future studies, including and combining multiple methods of ascertaining diagnostic status, such as single-item, algorithm-based, and EHR data, may yield more robust phenotypes and increase power for analyses (21).…”

“…Other researchers have argued that broad depression phenotyping shows the same genetic overlap with neuroticism and therefore is not specific to MDD (8). Algorithm-based MDD has also been found to have significantly higher heritability than single-item MDD, suggesting that utilising the single-item measure could decrease the power to detect genetic effects despite the increase in sample size (8,21). These reduced heritability estimates could be partially explained by the low sensitivity of single-item for algorithm-based MDD and any anxiety, as misclassification dilutes the power of case-control analyses to detect differences between the samples (22,23).…”

“…These reduced heritability estimates could be partially explained by the low sensitivity of single-item for algorithm-based MDD and any anxiety, as misclassification dilutes the power of case-control analyses to detect differences between the samples (22,23). Combining multiple broad phenotyping measures (e.g., single-item diagnoses, single-item help-seeking questions, and self-reported antidepressant usage) has been shown to reduce misclassification and increase heritability of MDD cases to equal or exceed heritability estimates of algorithm-based MDD in the UK Biobank (21).…”

Investigating pleiotropy between depression and autoimmune diseases using the UK Biobank

“…We created two depression case groups: strictly-defined cases termed ‘stringent depression’ and liberally-defined cases termed ‘any depression’. We have previously shown that SNP-based heritability increases with multiple endorsements of depression 16 . We therefore classified ‘stringent depression’ as participants endorsing at least three of the following depression measures: ICD-10 diagnoses (F32-F33.9); self-reported depression; self-reported antidepressant usage; single or recurrent depression (defined by Smith, et al 17 from responses to a touchscreen questionnaire completed at baseline by 172,751 participants); or answered ‘yes’ to the touchscreen questionnaire: “Have you ever seen a GP/psychiatrist for nerves, anxiety, tension or depression?”.…”

“…Detail on the derivation of each indication of depression, schizophrenia and bipolar can be found in Supplementary Materials from our previous publication 16 .…”