Hiroshi Okuda1,2,3, Koji Okamoto4,5, Michiaki Abe1,2,3, Kota Ishizawa1,2, Satoshi Makino2, Osamu Tanabe2,6, Junichi Sugawara2, Atsushi Hozawa2, Kozo Tanno7, Makoto Sasaki7, Gen Tamiya2,8, Masayuki Yamamoto2, Sadayoshi Ito2,3, Tadashi Ishii1,2. 1. Department of Education and Support for Regional Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. 2. Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8573, Japan. 3. Department of Nephrology, Endocrinology and Vascular Medicine, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. 4. Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8573, Japan. okamoto5-tky@umin.ac.jp. 5. Department of Nephrology, Endocrinology and Vascular Medicine, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. okamoto5-tky@umin.ac.jp. 6. Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima, Hiroshima, 732-0815, Japan. 7. Iwate Tohoku Medical Megabank Organization, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. 8. RIKEN Center for Advanced Intelligence Project Nihonbashi, 1-chome Mitsui Bldg. 15F, 1-4-1 Nihonbashi, Chuo-ku, Tokyo, 103-0027, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 10-10)]. CONCLUSION: In this study, we successfully identified UAE-associated variant loci in the Japanese population. Further study is required to confirm this association.
BACKGROUND: 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. METHODS: 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. RESULTS: 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 × 10-10)]. CONCLUSION: In this study, we successfully identified UAE-associated variant loci in the Japanese population. Further study is required to confirm this association.
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