An ImmunoChip study of multiple sclerosis risk in African Americans

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10–4), one of which (rs2702180) also showed nominally significant evidence for ass...

Source: Brain - May 26, 2015 Category: Neurology Authors: Isobe, N., Madireddy, L., Khankhanian, P., Matsushita, T., Caillier, S. J., More, J. M., Gourraud, P.-A., McCauley, J. L., Beecham, A. H., International Multiple Sclerosis Genetics Consortium, Piccio, L., Herbert, J., Khan, O., Cohen, J., Stone, L., Santa Tags: Original Articles Source Type: research