台灣腎結石病人之全基因組關聯分析

李明儒、李永進、詹鎮豪、王巽玄、沈榮宗、曹曜軒、黃書彬、吳怡萱、耿俊閎

¹高雄市立小港醫院 泌尿部；²高雄醫學大學附設醫院 泌尿部；³高雄醫學大學 醫學系；
⁴高雄醫學大學 臨床醫學研究所；⁵高雄醫學大學 環境醫學中心

A Genome-Wide Association Study (GWAS) of Kidney Stone Disease
in the Taiwanese Population.

Ming-Ru Lee^1,2,3, Yung-Chin Lee^1,2,3, Jhen-Hao Jhan^1,2,3, Hsun-Shuan Wang^1,2,3, Jung-Tsung Shen¹, Yao-Hsuan Tsao^1,2,3, Shu-Pin Huang^2,3,4,5, Yi-Hsuan Wu^1,2,3,4,Jiun-Hung Geng^1,2,3,4,5,

¹ Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan, ² Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ³ Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ⁴ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ⁵ Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Purpose: Inherited genetic factors are among the variables influencing the development of kidney stone disease (KSD). We conducted a genome-wide association study (GWAS) to identify germline genetic polymorphisms associated with KSD in a large-scale community-based cohort in Taiwan.

Materials and Methods: DNA isolated from blood from 122,067 subjects in the Taiwan Biobank were genotyped for approximately 500,000 single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05. An additional 90 million SNPs per sample were imputed using data from the 1000 Genomes Project. The presence of kidney stone disease was defined by self-reported history of kidney stones.

Results: The mean age of participants was 50 years old, and 64% were female. Self-reported kidney stones were observed in 7,738 (6%) participants. We identified 132 susceptibility loci reaching a genome-wide threshold of P < 5.0x10⁻⁸. The SNPs most highly associated with KSD were polymorphisms residing in intronic regions of the genes DGKH and ABCG2.

Conclusion: Our data identified 132 loci near DGKH and ABCG2, on 13q42.11 and 4q122.1 respectively, are associated with development of KSD. Reproducibility needs to be assessed in an independent cohort. Proven associations with KSD will provide novel insights into KSD as well as potential clinical biomarkers.