TY - JOUR T1 - The stratification of major depressive disorder into genetic subgroups JF - bioRxiv DO - 10.1101/134601 SP - 134601 AU - David M. Howard AU - Toni-Kim Clarke AU - Mark J. Adams AU - Jonathan D. Hafferty AU - Eleanor M. Wigmore AU - Yanni Zeng AU - Lynsey S. Hall AU - Jude Gibson AU - Thibaud S. Boutin AU - Caroline Hayward AU - Pippa A. Thomson AU - David J. Porteous AU - Blair H. Smith AU - Alison D. Murray AU - Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium AU - Chris S. Haley AU - Ian J. Deary AU - Heather C. Whalley AU - Andrew M. McIntosh Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/05/134601.abstract N2 - 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. ER -