RT Journal Article SR Electronic T1 The stratification of major depressive disorder into genetic subgroups JF bioRxiv FD Cold Spring Harbor Laboratory SP 134601 DO 10.1101/134601 A1 David M. Howard A1 Toni-Kim Clarke A1 Mark J. Adams A1 Jonathan D. Hafferty A1 Eleanor M. Wigmore A1 Yanni Zeng A1 Lynsey S. Hall A1 Jude Gibson A1 Thibaud S. Boutin A1 Caroline Hayward A1 Pippa A. Thomson A1 David J. Porteous A1 Blair H. Smith A1 Alison D. Murray A1 Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium A1 Chris S. Haley A1 Ian J. Deary A1 Heather C. Whalley A1 Andrew M. McIntosh YR 2017 UL http://biorxiv.org/content/early/2017/05/05/134601.abstract AB Major depressive disorder (MDD) is a heritable condition (h2 = 37%)1 and a leading cause of disability worldwide2. MDD is clinically heterogeneous and comorbid with a variety of conditions and it has been hypothesised that this causal heterogeneity may have confounded previous attempts to elucidate its genetic architecture3-5. We applied a relatively new technique, Buhmbox6, to identify the presence of heterogeneous sub-groups within MDD using summary data from genome-wide association studies. We analysed two independent cohorts (ntotal = 31,981) and identified significant evidence (Pcorrected < 0.05) for 10 sub-groups across both cohorts, including subgroups with a liability for migraine, alcohol consumption and eczema. The most notable subgroups (Pcorrected ≤ 2.57 × 10−8 in both cohorts) were for blood levels of cholesterol and triglycerides, and blood pressure, indicating subgroups within MDD cases of individuals with a genetic predisposition for anomalous levels of these metabolic traits. Our findings provide strong evidence for novel causal heterogeneity of MDD and identify avenues for both stratification and treatment.