Approximately 110 multiple genetic variations were previously identified by genome-wide association studies (GWAS) to be associated with Multiple Sclerosis (MS). Now, that number has increased, with more than 159 genetic variants identified, thanks to new research presented by Philip De Jager, M.D., of Brigham and Women’s Hospital, Harvard Medical School and the International MS Genetics Consortium at the ACTRIMS-ECTRIMS conference in Boston.
The team led by Dr. De Jager performed the first comprehensive meta-analysis of existing MS-GWAS, spanning approximately 14,000 individuals with the disease. The researchers identified unknown genetic variants, and further studies involving 2,000 individuals led to confirmation of 48 new variants — for now.
With the confirmed identification of these new genetic variants, the team proposed to understand how the variants relate to MS susceptibility. Dr. De Jager noted, “the majority of the MS genes seemed to be related to immune function and expressed on immune cells.” The authors hypothesized the new variants could be related with alterations to brain function. To test their hypothesis, they examined the newly genetic variants in older, MS-free postmortem frontal lobes’ tissues. “[This is] exciting because there are at least some disease effects that may be related to alteration of gene expression inside the brain,” commented the author. Since the analysis was performed with the whole tissue, at the moment the authors can’t confirm the source cell type for these genes, as Dr De Jager noted, “Some of these changes may be driven by changes in the brain’s immune cells like changes in the microglia.”
Notably, Dr. De Jager highlighted how certain genome regions harbor multiple different variants that impact the risk for MS. Hence, to develop reliable predictive tests for MS, it is crucial to study each of these variants and fully understand their functional impact on MS.
The current study explains less than half of the heritability of MS, so Dr. De Jagers’ team and the International MS Genetics Consortium are committed to identify more genetic variants for MS susceptibility and to study it thoroughly.