[Online phenotypes of depression symptoms are associated with polygenic risk scores of somatic diseases in a population-based cohort].

OBJECTIVE

To test an associations of online phenotypes of depressive symptoms with polygenic risk scores (PRS) for selected somatic diseases in a population-based cohort.

MATERIAL AND METHODS

Participants in a Russian population-based cohort (=4520) underwent online phenotyping based on the originally developed questionnaire using DSM-5 criteria (DSM phenotypes) and the Hospital Anxiety and Depression Scale (HADS) questionnaire (HADS phenotypes). After DNA genotyping with microarrays, PRS were calculated using summary statistics from large-scale GWASs (mostly from UK Biobank) for irritable bowel syndrome (IBS), coronary heart disease (narrow and broad phenotypes) (CHD), ischemic stroke (IS),diabetes mellitus type 2 (DT2) and migraine (MG). Then we assessed associations of PRS for somatic diseases with online phenotypes of depressive symptoms in a population-based cohort.

RESULTS

Highly specific associations of PRS for somatic diseases with online phenotypes of depressive symptoms in a population cohort were identified: positive associations of PRS IBS with «DSM depression» (=0.0035) and PRS CHD (narrow phenotype) with «DSM bipolar disorder» (=0.0207), as well as a negative association of PRS IS with the symptomatic DSM phenotype «Hyperphagia» (=0.0262). All the HADS phenotypes (clinical depression, subclinical depression, and HADS-D total score) showed a positive association with PRS for IBS and DT2, and at the same time were negatively associated with PRS IS. The DSM phenotype «Hypersomnia and hyperphagia» was positively associated with PRS for DT2 and IS, and negatively associated with PRS CHD (narrow phenotype). The DSM phenotypes «Subclinical Depression», «Hypersomnia», and «Anhedonia» showed exclusively negative associations with PRSs for DT2, IS, and IBS. Three maximum informative PRS by explained variance (PRS.R2) were found for the single DSM phenotype «Hypersomnia and hyperphagia»: PRS for IS and DT2 are positively associated and increase the risk of this phenotype, and PRS CHD (narrow phenotype) has a negative association and reduces the risk of this phenotype.

CONCLUSION

Our study confirmed the presence of possible genetic comorbidity of depression and chronic somatic diseases and showed different effectiveness of online phenotyping of depressive symptoms as markers of genetic risk of somatic diseases in the population cohort. Further research is needed to construct various versions of online phenotyping test systems for population-based screening of cohorts at high genetic risk for genetically comorbid diseases.