SAN DIEGO — A very large genetic linkage study has pinpointed the major histocompatibility complex on the short arm of chromosome 6 as the key genetic player in multiple sclerosis.
The study is not the first to implicate the major histocompatibility complex (MHC), a cluster of genes critical to the recognition of the body's own cells as “self.”
However, this study is the largest and most definitive to date, and its findings call into question data from smaller studies that suggested critical roles for other genetic regions.
Jonathan Haines, Ph.D., of Vanderbilt University, Nashville, Tenn., presented the findings on behalf of the International Multiple Sclerosis Genetics Consortium.
The team typed 4,506 single nucleotide polymorphism markers in 730 families who had more than one family member with multiple sclerosis.
Subjects were from Australia, Scandinavia, the United Kingdom, and the United States. Genes from 945 pairs of relatives were studied for genetic linkages.
“Highly significant linkage is observed in the region of the MJC ([linkage analysis] logarithm of the odds score 11.7), and suggestive linkage is found on chromosomes 17 and 5,” Dr. Haines stated in a poster presented at the annual meeting of the American Neurological Association.
An ordered subset analysis identified a further locus on chromosome 19.
The mean information extraction from the marker panel is 80%, with a range of 42%–91%, Dr. Haines reported.
Observed Mendelian inconsistencies suggest that within the data set, the genotyping error rate was just 0.002%.
“Our results confirm the strong role of the major histocompatibility complex genes in MS, and provide a definitive statement that no other region of the genome harbors a gene with a similar overall influence on MS genetics,” Dr. Haines said in a statement released at the meeting.
“Other genes may still play an important role in MS but finding them will require using new genomic techniques,” he added.
Dr. Haines said the findings have “profound implications for the future directions of multiple sclerosis genetics research and suggest that previous efforts in this area are almost all substantially underpowered.”
Future association studies should include at least 500–1,000 cases of multiple sclerosis to be considered reliable, he said.