It is well established that multiple sclerosis is a heritable disease. Nevertheless, the susceptibility genes for this common condition have so far eluded researchers. Two studies reported in Nature Genetics now take us a step closer to unravelling the genetic risk factors that underlie this disorder.

The only known genomic region that has been linked to multiple sclerosis is the major histocompatibility complex (MHC) on chromosome 6, a large region that is involved in immune responses. Lincoln and colleagues used this as the starting point for their large-scale search for multiple sclerosis risk genes.

These researchers genotyped two independent samples of individuals with multiple sclerosis from Canada and Finland using a dense panel of single nucleotide polymorphisms (SNPs) that cover the MHC region. They confirmed the associations between this genomic region and multiple sclerosis. Moreover, they narrowed the candidate region to HLA-DRB1 as the most promising susceptibility locus.

In the second study, Reich and colleagues used high-powered admixture mapping — a technique that identifies genomic regions with disease genes by exploiting differences in genetic marker frequency among different populations. Populations with combined ancestry have different frequencies of susceptibility genes that reflect the extent to which each original population has contributed to each individual's genome. As multiple sclerosis is more prevalent among European Americans than African Americans, genomic regions that contain risk genes would therefore be associated with a greater European than African contribution in African American individuals with multiple sclerosis.

Reich et al. studied a large group of African Americans and found a strong association between the extent of European ancestry and multiple sclerosis around the centromere of chromosome 1. However, they did not discover admixture associations elsewhere on the genome, including the MHC region.

Although further large-scale studies will be required to reconcile these findings and to further refine our knowledge of the particular genes that confer risk for multiple sclerosis, these studies highlight promising candidates for future exploration. Moreover, the success of admixture mapping suggests that it could be a powerful tool for identifying genetic risk factors in other complex disorders.