Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans.
Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans.
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DOI：
10.1038/s41598-020-74035-7
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发表时间：
2020-10-09
影响因子：
4.6
通讯作者：
Reich D
中科院分区：
文献类型：
--
作者：
Nakatsuka N;Patterson N;Patsopoulos NA;Altemose N;Tandon A;Beecham AH;McCauley JL;Isobe N;Hauser S;De Jager PL;Hafler DA;Oksenberg JR;Reich D
流行病学研究表明，欧洲血统的个体与非洲血统的个体相比，多发性硬化症（MS）的发病率存在差异，这促使基因扫描识别可能导致这种模式的变异。在对899例非裔美国人和1155例非裔美国人的全基因组扫描中，我们证实，在1号染色体位点继承欧洲血统基因组片段的非裔美国人患多发性硬化症的风险增加[LOD = 9.8]，尽管当增加406例时信号减弱，反映了两组病例的异质性[LOD = 2.7]。899个个体的关联可以用两个先前与欧洲血统个体的多发性硬化症相关的变异来完全解释。这些变异标记了一种与CD58基因表达减少相关的MS易感性单倍型（优势比为1.37，欧洲人的频率为84%，西非人的频率为22%）以及另一种靠近FCRL3基因的单倍型（优势比为1.07，欧洲人的频率为49%，西非人的频率为8%）。在控制了所有其他遗传和环境因素后，这两种变异预测欧裔美国人患多发性硬化症的几率比非裔美国人高1.44倍。
Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.
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