SA44 - THE IDENTIFICATION OF HETEROGENEOUS GENETIC SUBGROUPS FOR MAJOR DEPRESSIVE DISORDER

Abstract

Background Major Depressive Disorder (MDD) is a leading cause of disability worldwide with an estimated heritability of 37%. MDD is clinically heterogeneous and has frequently been shown to be comorbid with a variety of other conditions. Both of these factors have potentially confounded previous attempts to elucidate MDD's genetic architecture. To investigate causal heterogeneity within MDD we sought to identify genetic subgroups associated with other traits within MDD cases. Methods We examined two cohorts comprising of unrelated individuals, Generation Scotland: Scottish Family Health Study (GS:SFHS; n=6,946) and UK Biobank (n=25,035), for evidence of heterogeneous genetic sub-groups within MDD cases. Within GS:SFHS, a diagnosis of MDD was made by trained researchers using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. UK Biobank participants completed a touchscreen assessment of depressive symptoms and previous treatments from which a probable diagnosis of MDD was determined. We obtained risk alleles for a total of 34 traits and used the software package Buhmbox to determine whether there was a sharing of risk alleles associated with each trait and a subgroup within our MDD cases. Results There was evidence (P Discussion As far as we are aware, ours is the first study to identify the existence of genetic subgroup heterogeneity within MDD. In our study, the strongest evidence of genetic subgroups within MDD cases were for blood pressure, cholesterol and triglyceride levels. Our study has provided replicable evidence of subgroup heterogeneity within MDD for a number of traits underlining the potential of using genomic data to develop stratified approaches for the diagnosis and treatment of depression.