Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping.
Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping.
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DOI：
10.1038/gene.2017.6
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发表时间：
2017-03
影响因子：
5
通讯作者：
Fowler VG Jr
中科院分区：
文献类型：
--
作者：
Cyr DD;Allen AS;Du GJ;Ruffin F;Adams C;Thaden JT;Maskarinec SA;Souli M;Guo S;Dykxhoorn DM;Scott WK;Fowler VG Jr
金黄色葡萄球菌菌血症(SAB)在非裔美国人(AA)中的发病率明显高于欧洲裔人群。我们使用混合作图(AM)来检验假设，即欧洲和非洲祖先基因组中不同频率的基因组变异影响AAS对SAB的易感性。对565例成人AA(390例SAB患者和175例年龄匹配的对照)进行AM基因分型。使用MIXSCORE计算仅病例混合评分和混合χ2(1DF)评分(MIX)，以联合评估单核苷酸多态和混合关联(P<；5.00e-08)。此外，实施了一种排列方案来获得多重性调整的P值(全基因组0.05显著阈值：P<；9.46e-05)。经经验性多态调整后，发现6号染色体上的一个区域(52个SNPs，P=4.56e-05)在欧洲血统中表现出全基因组的显著增加。该区域编码参与人类白细胞抗原介导的免疫反应的基因，这些结果为基因变异影响人类白细胞抗原介导的免疫，调节对SAB的易感性提供了额外的证据。
The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ2(1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P<5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P<9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.