UK Biobank Replication Study using Bionic and GWAS data

The original proposal entitled ‘Disentangling the genetics of depression and anxiety; add-on study in Lifelines’ describes an add-on study to collect data on lifetime major depression, with the aim of investigating the heterogeneity of Major Depression (MD) . The current proposed additional analysis focuses on the genetic heterogeneity of MD. Specifically, the current proposed additional analysis will focus on investigating MD and its symptoms from the DSM diagnosis1, specifically the 14 disaggregated symptoms, data that resulted from the previous proposal and add-on study.2 The authors describe that due to the polygenic nature and heterogeneous makeup of the MD diagnosis patient profiles differ greatly between individuals. Current literature theory suggests an explanatory theory where MD is most likely the outcome of diverse and potentially interacting pathways.3,4 However, this remains to be robustly demonstrated. Therefore, in this project we set out to test for polygenic interactions between the underlying pathways of MD and its symptoms. Our preliminary results show significant polygenic interactions within the UK Biobank for both LifetimeMDD ( p=9.5e-12), and 10 out of 14 symptoms show significant interactions. The current request for additional analysis in Lifelines aims to replicate these results, thereby strengthening our findings.