Whether major mood disorders, such as bipolar disorder and clinical depression, are the result of heritage or environmental factors has been a point of contention for some time now. Studies in the recent past have encountered difficulties mapping the differences in the genetic profiles between those affected by individual major mood disorders and others who are not. A new meta-analysis in Nature has widened the scope of study by looking at two major mood disorders at once, and by doing so, have found that individuals with either disorder tend to carry a certain allele on the same gene.

Similarities between major mood disorders, such as treatments, shared familial risk, and the concordance of a disorder between sets of twins, are considered to be evidence that the major mood disorders arise from at least some similar genetic factors. Studies done on major mood disorders typically concern themselves with one disorder at a time, such as major depressive disorder, but often don't turn up conclusive evidence about which genes might be causing problems.

To overcome this, researchers did a meta-analysis of five studies on the genetics of major mood disorders, all conducted on individuals of European ancestry who had been diagnosed, genotyped, and compared to control groups without major mood disorders. They then compared the results of this analysis to three other independently-conducted studies on single disorders to see if their findings held up.

The analysis took data from a few different sources, including the National Institute of Mental Health and the Wellcome Trust Case Control Consortium. The studies looked specifically at single nucleotide polymorphisms (SNPs), or places where the DNA sequence varied one nucleotide—for example, a sequence consisting of a string of alleles like AAGA instead of AAAA.

In the studies, researchers found that there were six SNPs on chromosome 3p21 that could be associated with the presence of a major mood disorder. At the most significant marker, rs2251219, the presence of a C allele was consistently less common in individuals with major mood disorders than in those without. Rotating out one study at a time and conducting the analysis on the remaining four studies gave consistent results.

The analysis' results were then compared those of three independent studies conducted by GlaxoSmithKline, one on bipolar disorder and two on major depressive disorder. Only the bipolar disorder study corroborated the lack of the appropriate C allele, and neither of the MDD studies found an association between rs2251219 and the diagnosis. However, one of the MDD studies showed that variations of markers physically near to rs2251219 were associated with MD, and when all three were included in the meta-anaylsis, and when the results of all three were included in the meta-analysis, their net effect was to increase the support for attributing major mood disorders to rs2251219.

Previous studies on major mood disorders have noted a few different gene variations, but this is the first study to show a relationship between the 3p chromosome and a psychiatric disorder. However, its researchers note that there is still a lot of work to be done—while there is now evidence of genetic overlap between depression and bipolar disorder, it does not explain why some carriers of the variation develop one and not the other, or else remain healthy. They speculate that each disorder may be the result of a combination of variations at a few different locations, as well as environmental influences or other external factors.

Nature, 2010. DOI: 10.1038/ng.523