Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Department of Human Genetics, Graduate School of Public Health (GSPH), University of Pittsburgh, Pittsburgh, PA, USA.
Dis Markers. 2020 Jul 31;2020:1910215. doi: 10.1155/2020/1910215. eCollection 2020.
Rheumatoid arthritis (RA) is a complex and multifactorial autoimmune disorder with the involvement of multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified more than 50 RA genetic loci in European populations. Given the anticipated overlap of RA-relevant genes and pathways across different ethnic groups, we sought to replicate 58 GWAS-implicated SNPs reported in Europeans in Pakistani subjects. 1,959 unrelated subjects comprising 1,222 RA cases and 737 controls were collected from three rheumatology facilities in Pakistan. Genotyping was performed using iPLEX or TaqMan® methods. A total of 50 SNPs were included in the final association analysis after excluding those that failed assay design/run or postrun QC analysis. Fourteen SNPs (/rs1516971, /rs2240336, /rs4409785, /rs3087243, /rs13426947, /rs2596565, /rs26232, /rs951005, /rs2275806, /rs595158, /rs660895, /rs3806624, /rs934734, and /rs9979383) were replicated in our Pakistani sample at false discovery rate (FDR) of <0.20 with nominal values ranging from 4.73-06 to 3.48-02. Our results indicate that several RA susceptibility loci are shared between Pakistani and European populations, supporting the role of common genes/pathways.
类风湿关节炎（RA）是一种复杂的多因素自身免疫性疾病，涉及多种遗传和环境因素。全基因组关联研究（GWAS）已经在欧洲人群中确定了 50 多个 RA 遗传位点。鉴于 RA 相关基因和途径在不同种族之间的预期重叠，我们试图在巴基斯坦受试者中复制欧洲人报告的 58 个 GWAS 提示的 SNP。从巴基斯坦的三个风湿病设施中收集了 1959 名无关受试者，包括 1222 例 RA 病例和 737 名对照。使用 iPLEX 或 TaqMan®方法进行基因分型。在排除那些未能通过检测设计/运行或运行后 QC 分析的 SNP 后，共有 50 个 SNP 纳入最终的关联分析。在我们的巴基斯坦样本中，有 14 个 SNP（/rs1516971、/rs2240336、/rs4409785、/rs3087243、/rs13426947、/rs2596565、/rs26232、/rs951005、/rs2275806、/rs595158、/rs660895、/rs3806624、/rs934734 和 /rs9979383）在错误发现率（FDR）<0.20 的情况下得到复制，名义 值范围从 4.73-06 到 3.48-02。我们的结果表明，RA 易感基因座在巴基斯坦和欧洲人群之间存在共享，支持共同基因/途径的作用。
