Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2012;7(2):e32338. doi: 10.1371/journal.pone.0032338. Epub 2012 Feb 23.
Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown.
METHODOLOGY/PRINCIPAL FINDINGS: We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls.
CONCLUSIONS/SIGNIFICANCE: Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations.
尽管非洲裔美国人的危险因素负担更大，但心房颤动 (AF) 的发病率却低于欧洲裔人群。针对欧洲裔人群的 AF 全基因组关联研究 (GWAS) 已经确定了三个与风险增加相关的主要基因组区域（1q21、4q25 和 16q22）。这些位点对非裔美国人的 AF 风险的贡献尚不清楚。
方法/主要发现：我们研究了来自范德比尔特-梅哈里 AF 登记处的 73 名非裔美国人 AF 患者和 71 名非裔美国对照者，这些对照者均无 AF 病史，包括心脏手术后。对与 AF 相关的三个区域的 148 个 SNP 进行了关联检验，其中 22 个 SNP 与 AF 显著相关（P<0.05）。在非裔美国人中，与 AF 关联最强的 SNP 既不同于欧洲裔人群中确定的索引 SNP，也与索引欧洲裔人群 SNP 无关（HapMap CEU 中的 r(2)<0.40）：1q21 rs4845396（比值比 [OR] 0.30，95%置信区间 [CI] 0.13-0.67，P=0.003）、4q25 rs4631108（OR 3.43，95% CI 1.59-7.42，P=0.002）和 16q22 rs16971547（OR 8.1，95% CI 1.46-45.4，P=0.016）。病例组（23.6%）和对照组（23.8%）的欧洲血统估计值相似。因此，每个区域中两个欧洲衍生染色体拷贝的概率在病例和对照组之间没有差异。
结论/意义：在已知的 AF 位点上可变的欧洲混合并不能解释非裔美国人中 AF 易感性降低。这些数据支持 1q21、4q25 和 16q22 变异在非裔美国人 AF 风险中的作用，尽管索引 SNP 与欧洲裔人群中的 SNP 不同。
