Department of Education and Support for Regional Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8573, Japan.
Clin Exp Nephrol. 2020 Aug;24(8):1-9. doi: 10.1007/s10157-020-01884-x. Epub 2020 Jul 20.
Urinary albumin excretion (UAE) is a risk factor for cardiovascular diseases, metabolic syndrome, chronic kidney disease, etc. Only a few genome-wide association studies (GWAS) for UAE have been conducted in the European population, but not in the Asian population. Here we conducted GWAS and identified several candidate genes harboring single nucleotide polymorphisms (SNPs) responsible for UAE in the Japanese population.
We conducted GWAS for UAE in 7805 individuals of Asian ancestry from health-survey data collected by Tohoku Medical Megabank Organization (ToMMo) and Iwate Tohoku Medical Megabank Organization (IMM). The SNP genotype data were obtained with a SNP microarray. After imputation using a haplotype panel consisting of 2000 genome sequencing, 4,962,728 SNP markers were used for the GWAS.
Eighteen SNPs at 14 loci (GRM7, EXOC1/NMU, LPA, STEAP1B/RAPGEF5, SEMA3D, PRKAG2, TRIQK, SERTM1, TPT1-AS1, OR5AU1, TSHR, FMN1/RYR3, COPRS, and BRD1) were associated with UAE in the Japanese individuals. A locus with particularly strong associations was observed on TSHR, chromosome 14 [rs116622332 (p = 3.99 × 10)].
In this study, we successfully identified UAE-associated variant loci in the Japanese population. Further study is required to confirm this association.
尿白蛋白排泄(UAE)是心血管疾病、代谢综合征、慢性肾脏病等的风险因素。仅有少数全基因组关联研究(GWAS)针对欧洲人群的 UAE 进行了研究,但未针对亚洲人群进行研究。在此,我们在日本人群中进行了 GWAS,并鉴定了一些与 UAE 相关的候选基因,这些基因中包含单核苷酸多态性(SNP)。
我们利用东北医疗巨型联盟组织(Tohoku Medical Megabank Organization,ToMMo)和岩手东北医疗巨型联盟组织(Iwate Tohoku Medical Megabank Organization,IMM)收集的健康调查数据,对 7805 名亚洲血统个体进行了 UAE 的 GWAS。SNP 基因型数据通过 SNP 微阵列获得。使用包含 2000 个全基因组测序的单体型面板进行 imputation 后,共使用了 4962728 个 SNP 标记进行 GWAS。
在日本个体中,14 个位点的 18 个 SNP(GRM7、EXOC1/NMU、LPA、STEAP1B/RAPGEF5、SEMA3D、PRKAG2、TRIQK、SERTM1、TPT1-AS1、OR5AU1、TSHR、FMN1/RYR3、COPRS 和 BRD1)与 UAE 相关。在 TSHR 染色体 14 上观察到一个具有特别强关联的位点[rs116622332(p=3.99×10)]。
在这项研究中,我们成功鉴定了日本人群中与 UAE 相关的变异位点。需要进一步的研究来确认这种关联。