Abstract
Depression is a common and clinically heterogeneous mental health disorder that is frequently comorbid with other diseases and conditions. Stratification of depression may align sub-diagnoses more closely with their underling aetiology and provide more tractable targets for research and effective treatment. In the current study, we investigated whether genetic data could be used to identify subgroups within people with depression using the UK Biobank. Examination of cross-locus correlations were used to test for evidence of subgroups using genetic data from seven other complex traits and disorders that were genetically correlated with depression and had sufficient power (>0.6) for detection. We found no evidence for subgroups within depression for schizophrenia, bipolar disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, anorexia nervosa, inflammatory bowel disease or obesity. This suggests that for these traits, genetic correlations with depression were driven by pleiotropic genetic variants carried by everyone rather than by a specific subgroup.
Highlights
Depression is a common mental health disorder characterised by persistent feelings of sadness or a loss of interest in day-to-day activities lasting for at least a 2week period
There is a genetic correlation of 0.33 between depression and bipolar disorder[13]. If this genetic correlation was due to pleiotropy, several of the bipolar disorder variants would be carried by most depression cases
The first phenotype analysed was based on the Composite International Diagnostic Interview Short Form (CIDI-SF)[18] as used by Davis et al.[16] to provide a lifetime instance measure of depression in the UK Biobank
Summary
Depression is a common mental health disorder characterised by persistent feelings of sadness or a loss of interest in day-to-day activities lasting for at least a 2week period. Twinbased studies[10] and genome-wide association studies[11,12] have shown depression to be heritable and genetically correlated with a number of other traits and disorders. This shared genetic component could be due to pleiotropic variants shared across all individuals but could be as a result of a subgroup for the other trait within depression cases. A subgroup could arise where there is a causal association, a shared
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