Genome-wide association study identifies new loci for albuminuria in the Japanese population

Hiroshi Okuda; Koji Okamoto; Michiaki Abe; Kota Ishizawa; Satoshi Makino; Osamu Tanabe; Junichi Sugawara; Atsushi Hozawa; Kozo Tanno; Makoto Sasaki; Gen Tamiya; Masayuki Yamamoto; Sadayoshi Ito; Tadashi Ishii

doi:10.1007/s10157-020-01884-x

Genome-wide association study identifies new loci for albuminuria in the Japanese population

Clin Exp Nephrol. 2020 Aug;24(8):1-9. doi: 10.1007/s10157-020-01884-x. Epub 2020 Jul 20.

Authors

Hiroshi Okuda^{1

2

3}, Koji Okamoto^{4

5}, Michiaki Abe^{1

2

3}, Kota Ishizawa^{1

2}, Satoshi Makino², Osamu Tanabe^{2

6}, Junichi Sugawara², Atsushi Hozawa², Kozo Tanno⁷, Makoto Sasaki⁷, Gen Tamiya^{2

8}, Masayuki Yamamoto², Sadayoshi Ito^{2

3}, Tadashi Ishii^{1

2}

Affiliations

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.

Keywords: Albuminuria; Cohort study; GWAS; Genetics; QTL; TSHR.

MeSH terms

Adult
Aged
Albuminuria / genetics*
Cohort Studies
Female
Genome-Wide Association Study
Humans
Japan
Male
Middle Aged
Polymorphism, Single Nucleotide
Tumor Protein, Translationally-Controlled 1
Young Adult