Two Groups Arrive at Same Location for Major-Depression Gene

Researchers at the Washington University School of Medicine's Department of Psychiatry recently went looking for the genetic linkage between heavy smoking and depression in Australian and Finnish families, but discovered something even bigger: the genetic location of major depressive disorder on chromosome 3.

In a surprising coincidence, researchers at King's College London's Institute of Psychiatry found the same location. Both groups have published their findings in the American Journal of Psychiatry, with the publications posted online May 15.

Credit: Washington University School of Medicine

The first group, led by Michele Pergadia, Ph.D., carried out genetic linkage analyses of DSM-IV-diagnosed major depressive disorder in two samples that are part of the Nicotine Addiction Genetics (NAG) project, an international consortium focused on tobacco dependence. "We used an affected sibling-pair design, in which at least two adult offspring per family reported a history of DSM-IV major depressive disorder, and tested for linkage," said the group in its report. "Results appear to confirm a genomewide significant linkage signal at chromosome 3p25-3p26."

The NAG linkage project enrolled participants at the Queensland Institute of Medical Research in Australia and the University of Helsinki in Finland. More than 90 percent of the participants from the Australian site were of Anglo-Celtic or Northern-European ancestry, and all of the participants from the Finnish site were of Finnish ancestry. Genetic linkage analyses were performed on the 91 Australian families in the project who had one or more affected sibling pairs concordant for a history of major depressive disorder (n=187). In the Finnish sample, only 25 families had one or more affected sibling pairs (n=33). Results were not replicated in the Finnish sample, but the researchers attributed that to the small number of Finnish affected sibling pairs, saying "the lack of confirmation in this particular sample is not unexpected."

A separate study was, however, able to replicate the results found in the Australian sample. At King's College London's Institute of Psychiatry, Gerome Breen, Ph.D., and colleagues sought to find loci for major depression via linkage analysis of a large sibling-pair sample. As part of the Depression Network Study, the authors conducted a genomewide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression. The authors identified genomewide significant linkage to chromosome 3p25-3p26, suggesting this is a new locus for severe recurrent depression.

"As we began to query other research groups about replication of findings, Breen's group replied, noting a remarkable replication of the linkage finding," Pergadia told Psychiatric News. "We were very excited to hear this because—as with any scientific finding, and particularly in genomic research—replication is the key to begin validating a finding and moving forward with the work."

Pergadia revealed her group's plans for the future, as well: "The samples from the Depression Network Study [by Breen and colleagues] came from families known to be affected by depression. Our samples came from heavy smokers, so one thing we would like to do is to better characterize these families, to learn more about their smoking and depression histories, and other disorders and environmental factors that might distinguish them, in addition to all of their genetic information in this area. We could also start by combining the data sets from the two studies to see whether this region of chromosome 3 continues to exert a significant effect."

The Breen study was supported by GlaxoSmithKline Research and Development. The Pergadia study was supported by a Center for Inherited Disease Research grant to fund genomewide association studies and by the European Union.

"A Genome-Wide Significant Linkage for Severe Depression on Chromosome 3: The Depression Network Study" is posted at <http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2011.10091342v1>.

"A3p26-3p25 Genetic Linkage Finding forDSM-IVMajor Depression in Heavy Smoking Families" is posted at <http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2011.10091319v1>.