What causes major depression? (360G-Wellcome-200176_Z_15_Z)

The objective of this proposal is to discover genetic loci that impact on risk for major depressive disorder (MDD). Our previous Wellcome funded work in China developed a consortium that delivered the first replicated genome-wide significant loci influencing MDD. We now want to take that success forward. Success depends on access to a large, suitably characterized, clinical sample. Of all common diseases, MDD requires most attention to the quality and nature of phenotyping. This is because MDD likely represents a broad neurobiological syndrome with multiple inter-locking etiologic pathways rather than a single disease entity with a clearly defined pathophysiology. We aim to collect 24,000 cases of recurrent major depression and 24,000 screened controls, using a collection strategy that maximizes clinical severity and homogeneity. Together with our existing sample of 12,000, the total sample will be 60,000, sufficent to identify at least 30 genetic risk loci. This will transform our understanding of the origins and nature of MDD, providing a starting point for improvements in mental health care.