Genetics Not a Predictor of Disease Severity in MS

Genetic analysis can assess the risk of getting multiple sclerosis (MS), but not how severe the disease would be, according to the results of a recent meta-analysis.

The analysis, conducted by Michaela George, PhD, of the University of California, Berkeley, and colleagues, was published in the journal Neurology Genetics on August 4, 2016.

The authors describe their objective, saying, “We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis.”

They used the multiple sclerosis severity score (MSSS) by using the Expanded Disability Status Scale, and analyzed 10 unique data sets.

A total of 7,125 cases were included in the analysis, making this the largest meta-analysis to date.

The authors say, “The strongest genetic risk factor is within the human leukocyte antigen (HLA)-DRB1 locus, specifically the 15:01 allele,” adding, “studies support the presence of additional independent susceptibility alleles within the major histocompatibility complex (MHC) Class I and Class II regions.”

But, those genes have not been shown to be associated with progression, and there are known environmental risk factors for MS.

“Through international collaboration, genome-wide association studies (GWAS) followed by replication have identified a large number of non-MHC MS risk variants,” report the researchers. This led them to hypothesize “that MS risk variants might also influence disease severity,” they say. They considered both a weighted genetic risk score (wGRS) and an unweighted genetic risk score (GRS) in the present analysis.

Due to the need for large, well-designed studies capable of detecting even modest genetic effects, there has been limited progress toward identifying disease-modifying genes in MS during the last 10 years or so. The researchers say, “The individuals included in this analysis are representative of the international MS population with regard to sex distribution, average age at onset, and proportion of HLA-DRB1*15:01 allele carriers.”

Although HLA-DRB1*15:01 has been shown to increase risk of MS, “it was not associated with disease severity here,” say the authors. Similarly, familial factors appear to not influence disease severity, however there is a clear need for additional studies “to identify or exclude genetic contributions to disease severity in MS,” according to the researchers.

The researchers conclude, “Results derived from investigation of a large number of recently established GWAS variants in 7,125 MS cases suggest that the genetics underlying MS susceptibility and disease severity, as measured by MSSS, do not substantially overlap.”

However, they also more data, specifically sensitive measures on severity and progression, and on larger cohort studies, is needed.

Further reading: