Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study

Asahi Hishida, Masahiro Nakatochi, Masato Akiyama, Yoichiro Kamatani, Takeshi Nishiyama, Hidemi Ito, Isao Oze, Yuichiro Nishida, Megumi Hara, Naoyuki Takashima, Tanvir Chowdhury Turin, Miki Watanabe, Sadao Suzuki, Rie Ibusuki, Ippei Shimoshikiryo, Yohko Nakamura, Haruo Mikami, Hiroaki Ikezaki, Norihiro Furusyo, Kiyonori KurikiKaori Endoh, Teruhide Koyama, Daisuke Matsui, Hirokazu Uemura, Kokichi Arisawa, Tae Sasakabe, Rieko Okada, Sayo Kawai, Mariko Naito, Yukihide Momozawa, Michiaki Kubo, Kenji Wakai

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. Methods: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. Results: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Conclusion: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

Original languageEnglish
Pages (from-to)304-316
Number of pages13
JournalAmerican Journal of Nephrology
Volume47
Issue number5
DOIs
Publication statusPublished - 01-06-2018

Fingerprint

Chromosomes, Human, Pair 18
Genome-Wide Association Study
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 2
Japan
Cohort Studies
Glomerular Filtration Rate
Chronic Renal Insufficiency
Chromosomes, Human, Pair 17
Creatinine
Kidney
Genetic Loci
Serum
Population
Genes
Low Density Lipoprotein Receptor-Related Protein-2
NFATC Transcription Factors
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 3
Meta-Analysis

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Hishida, Asahi ; Nakatochi, Masahiro ; Akiyama, Masato ; Kamatani, Yoichiro ; Nishiyama, Takeshi ; Ito, Hidemi ; Oze, Isao ; Nishida, Yuichiro ; Hara, Megumi ; Takashima, Naoyuki ; Turin, Tanvir Chowdhury ; Watanabe, Miki ; Suzuki, Sadao ; Ibusuki, Rie ; Shimoshikiryo, Ippei ; Nakamura, Yohko ; Mikami, Haruo ; Ikezaki, Hiroaki ; Furusyo, Norihiro ; Kuriki, Kiyonori ; Endoh, Kaori ; Koyama, Teruhide ; Matsui, Daisuke ; Uemura, Hirokazu ; Arisawa, Kokichi ; Sasakabe, Tae ; Okada, Rieko ; Kawai, Sayo ; Naito, Mariko ; Momozawa, Yukihide ; Kubo, Michiaki ; Wakai, Kenji. / Genome-Wide Association Study of Renal Function Traits : Results from the Japan Multi-Institutional Collaborative Cohort Study. In: American Journal of Nephrology. 2018 ; Vol. 47, No. 5. pp. 304-316.
@article{1fb8007725e44600b933727dadf0ccf6,
title = "Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study",
abstract = "Background: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. Methods: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. Results: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Conclusion: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.",
author = "Asahi Hishida and Masahiro Nakatochi and Masato Akiyama and Yoichiro Kamatani and Takeshi Nishiyama and Hidemi Ito and Isao Oze and Yuichiro Nishida and Megumi Hara and Naoyuki Takashima and Turin, {Tanvir Chowdhury} and Miki Watanabe and Sadao Suzuki and Rie Ibusuki and Ippei Shimoshikiryo and Yohko Nakamura and Haruo Mikami and Hiroaki Ikezaki and Norihiro Furusyo and Kiyonori Kuriki and Kaori Endoh and Teruhide Koyama and Daisuke Matsui and Hirokazu Uemura and Kokichi Arisawa and Tae Sasakabe and Rieko Okada and Sayo Kawai and Mariko Naito and Yukihide Momozawa and Michiaki Kubo and Kenji Wakai",
year = "2018",
month = "6",
day = "1",
doi = "10.1159/000488946",
language = "English",
volume = "47",
pages = "304--316",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",
number = "5",

}

Hishida, A, Nakatochi, M, Akiyama, M, Kamatani, Y, Nishiyama, T, Ito, H, Oze, I, Nishida, Y, Hara, M, Takashima, N, Turin, TC, Watanabe, M, Suzuki, S, Ibusuki, R, Shimoshikiryo, I, Nakamura, Y, Mikami, H, Ikezaki, H, Furusyo, N, Kuriki, K, Endoh, K, Koyama, T, Matsui, D, Uemura, H, Arisawa, K, Sasakabe, T, Okada, R, Kawai, S, Naito, M, Momozawa, Y, Kubo, M & Wakai, K 2018, 'Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study', American Journal of Nephrology, vol. 47, no. 5, pp. 304-316. https://doi.org/10.1159/000488946

Genome-Wide Association Study of Renal Function Traits : Results from the Japan Multi-Institutional Collaborative Cohort Study. / Hishida, Asahi; Nakatochi, Masahiro; Akiyama, Masato; Kamatani, Yoichiro; Nishiyama, Takeshi; Ito, Hidemi; Oze, Isao; Nishida, Yuichiro; Hara, Megumi; Takashima, Naoyuki; Turin, Tanvir Chowdhury; Watanabe, Miki; Suzuki, Sadao; Ibusuki, Rie; Shimoshikiryo, Ippei; Nakamura, Yohko; Mikami, Haruo; Ikezaki, Hiroaki; Furusyo, Norihiro; Kuriki, Kiyonori; Endoh, Kaori; Koyama, Teruhide; Matsui, Daisuke; Uemura, Hirokazu; Arisawa, Kokichi; Sasakabe, Tae; Okada, Rieko; Kawai, Sayo; Naito, Mariko; Momozawa, Yukihide; Kubo, Michiaki; Wakai, Kenji.

In: American Journal of Nephrology, Vol. 47, No. 5, 01.06.2018, p. 304-316.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-Wide Association Study of Renal Function Traits

T2 - Results from the Japan Multi-Institutional Collaborative Cohort Study

AU - Hishida, Asahi

AU - Nakatochi, Masahiro

AU - Akiyama, Masato

AU - Kamatani, Yoichiro

AU - Nishiyama, Takeshi

AU - Ito, Hidemi

AU - Oze, Isao

AU - Nishida, Yuichiro

AU - Hara, Megumi

AU - Takashima, Naoyuki

AU - Turin, Tanvir Chowdhury

AU - Watanabe, Miki

AU - Suzuki, Sadao

AU - Ibusuki, Rie

AU - Shimoshikiryo, Ippei

AU - Nakamura, Yohko

AU - Mikami, Haruo

AU - Ikezaki, Hiroaki

AU - Furusyo, Norihiro

AU - Kuriki, Kiyonori

AU - Endoh, Kaori

AU - Koyama, Teruhide

AU - Matsui, Daisuke

AU - Uemura, Hirokazu

AU - Arisawa, Kokichi

AU - Sasakabe, Tae

AU - Okada, Rieko

AU - Kawai, Sayo

AU - Naito, Mariko

AU - Momozawa, Yukihide

AU - Kubo, Michiaki

AU - Wakai, Kenji

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. Methods: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. Results: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Conclusion: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

AB - Background: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. Methods: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. Results: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. Conclusion: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

UR - http://www.scopus.com/inward/record.url?scp=85047435619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047435619&partnerID=8YFLogxK

U2 - 10.1159/000488946

DO - 10.1159/000488946

M3 - Article

AN - SCOPUS:85047435619

VL - 47

SP - 304

EP - 316

JO - American Journal of Nephrology

JF - American Journal of Nephrology

SN - 0250-8095

IS - 5

ER -