2024-03-29T15:41:13Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00026347
2023-01-16T04:16:48Z
499:500:501
Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study
Hishida, Asahi
85167
Nakatochi, Masahiro
85168
Akiyama, Masato
85169
Kamatani, Yoichiro
85170
Nishiyama, Takeshi
85171
Ito, Hidemi
85172
Oze, Isao
85173
Nishida, Yuichiro
85174
Hara, Megumi
85175
Takashima, Naoyuki
85176
Turin, Tanvir Chowdhury
85177
Watanabe, Miki
85178
Suzuki, Sadao
85179
Ibusuki, Rie
85180
Shimoshikiryo, Ippei
85181
Nakamura, Yohko
85182
Mikami, Haruo
85183
Ikezaki, Hiroaki
85184
Furusyo, Norihiro
85185
Kuriki, Kiyonori
85186
Endoh, Kaori
85187
Koyama, Teruhide
85188
Matsui, Daisuke
85189
Uemura, Hirokazu
85190
Arisawa, Kokichi
85191
Sasakabe, Tae
85192
Okada, Rieko
85193
Kawai, Sayo
85194
Naito, Mariko
85195
Momozawa, Yukihide
85196
Kubo, Michiaki
85197
Wakai, Kenji
85198
Chronic kidney disease
Genome-wide association study
Population-based cohort
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.
ファイル公開:2019/06/01
journal article
Karger
2018-06
application/pdf
American Journal of Nephrology
5
47
304
316
0250-8095
1421-9670
https://nagoya.repo.nii.ac.jp/record/26347/files/e319d920-d987-41e1-a462-1748be7fc9c8.pdf
eng
https://doi.org/10.1159/000488946
This is the accepted manuscript version of an article published by S. Karger AG in [American Journal of Nephrology/2018/47/5/304-316 DOI:10.1159/000488946] including DOI and available on https://doi.org/10.1159/000488946.