Genetic studies have recently yielded large numbers of "hits" for genes that subtly increase or decrease risk for disorders, including for schizophrenia. However, there have been no hits for major depression, perhaps because the studies are not yet large enough or because depression is less heritable. Estimates put the heritability of major depression at around 50%, with the remaining contribution coming from environmental and experiential causes.

However, a new approach has paid off: a study published online July 15th at the journal Nature identifies two genomic regions that harbor genes that increase risk of major depression. A multinational collaboration employed a strategy of narrowing the pool of subjects to women in China with the most severe and stubborn form of depression, with the hope that a more homogenous population would yield results.

In an accompanying News and Views, 2014 Lieber Prizewinner for Outstanding Achievement in Schizophrenia Research, Patrick Sullivan, M.D., of the University of North Carolina, writes, "This first identification of replicable, significant genome-wide associations for MDD is exceptional."

Qi Xu, Ph.D., of Peking Union Medical College and Jun Wang, Ph.D., of BGI-Shenzhen, who led the China components of the study, along with Foundation Scientific Council Member Kenneth Kendler, M.D., of Virginia Commonwealth University and 2007 NARSAD Distinguished Investigator Grantee Jonathan Flint, M.D., of the University of Oxford in the United Kingdom focused exclusively on women with severe, recurrent depression (an average of more than five episodes), building a sample of 5,303 cases and 5,337 controls. The results were replicated in a separate group of 3,231 Chinese women with major depression and 3,186 mixed male/female controls.

"I think this paper is groundbreaking because it really demonstrates that we can make progress in reducing genetic heterogeneity by paying attention to key clinical indicators," said three-time NARSAD Grantee, Francis McMahon, M.D., of the National Institute of Mental Health (NIMH), who was not an author on the paper.

Read more about this research on the Schizophrenia Research Forum.