Research Article

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

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Science  27 Sep 2019:
Vol. 365, Issue 6460, eaav7188
DOI: 10.1126/science.aav7188

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Genetic roots of multiple sclerosis

The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis.

Science, this issue p. eaav7188; see also p. 1383

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