Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
David M. Howard
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, UK
Oliver Pain
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Ken B. Hanscombe
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Bradley Jermy
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Ryan Arathimos
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Gerome Breen
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK
Paul F. O'Reilly
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; and Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, USA
Cathryn M. Lewis
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, King's College London, UK; and Department of Medical & Molecular Genetics, King's College London, UK
Background 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. Aims To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD). Method 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. Results 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. 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 UK Biobank data.
