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Multiple sclerosis susceptibility alleles in African Americans

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene–environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06–1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry.

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Acknowledgements

We thank the MS patients and controls that participated in this study. We thank L Piccio for her effort in the recruitment of study participants and sample management. We thank RR Lincoln, R Guerrero, H Mousavi, and A Santaniello for sample and database management. We thank R Gomez for recruitment of participants. We also thank J McElroy for insightful discussions. This work was funded by grants from the National Institute of Health (R01 NS046297) and the National Multiple Sclerosis Society (RG3060C8). PLD is a Harry Weaver Neuroscience Scholar Award of the National MS Society.

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Correspondence to J R Oksenberg.

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Johnson, B., Wang, J., Taylor, E. et al. Multiple sclerosis susceptibility alleles in African Americans. Genes Immun 11, 343–350 (2010). https://doi.org/10.1038/gene.2009.81

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