Jin Eun Hyo, Park Boram, Kim Young Sun, Choe Eun Kyung, Choi Seung Ho, Kim Joo Sung, Jung Sung-Ae
Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
Department of Public Health Sciences, Seoul National University, Seoul, Korea.
Clin Transl Gastroenterol. 2020 Mar;11(3):e00145. doi: 10.14309/ctg.0000000000000145.
The male-predominant sex difference through the spectrum of erosive esophagitis to Barrett's esophagus is widely known. We conducted a genome-wide association study (GWAS) stratified by sex for identifying factors that can predict the endoscopically diagnosed erosive esophagitis.
Erosive esophagitis was diagnosed by endoscopy and assessed for severity. We identified genetic factors associated with erosive esophagitis that accounted for the sex differences in a cohort of 4,242 participants via a GWAS. After quality control and imputation, genetic associations with erosive esophagitis were investigated by multivariate linear regression in 3,620 subjects. Single-nucleotide polymorphisms (SNPs) with P < 5.0 × 10 were considered significant genome wide, and a genetic risk score was constructed for the prediction of erosive esophagitis risk.
Six genome-wide significant SNPs near the GRIK2 gene on chromosome 6 were found to be associated with erosive esophagitis only in male subjects. These were predictive of severity through a genetic risk score (P < 0.05), and the findings were validated in a cohort of 622 subjects (P < 0.05).
This is the first GWAS of erosive esophagitis, and we identified 6 genome-wide significant SNPs in male subjects. These SNPs could help explain the pathogenesis of erosive esophagitis and contribute to the understanding of sex differences. Further genetic investigation could allow for the prediction of high risk for erosive esophagitis and development of new treatment options.
从糜烂性食管炎到巴雷特食管的男性为主的性别差异广为人知。我们进行了一项按性别分层的全基因组关联研究（GWAS），以确定可预测内镜诊断的糜烂性食管炎的因素。
通过内镜检查诊断糜烂性食管炎并评估其严重程度。我们通过GWAS在4242名参与者的队列中确定了与糜烂性食管炎相关的遗传因素，这些因素解释了性别差异。经过质量控制和归因后，在3620名受试者中通过多变量线性回归研究了与糜烂性食管炎的遗传关联。P<5.0×10的单核苷酸多态性（SNP）被认为在全基因组范围内具有显著性，并构建了遗传风险评分以预测糜烂性食管炎风险。
在6号染色体上的GRIK2基因附近发现6个全基因组显著的SNP仅与男性受试者的糜烂性食管炎相关。通过遗传风险评分，这些SNP可预测严重程度（P<0.05），并且在622名受试者的队列中得到了验证（P<0.05）。
这是首次对糜烂性食管炎进行的GWAS研究，我们在男性受试者中鉴定出6个全基因组显著的SNP。这些SNP有助于解释糜烂性食管炎的发病机制，并有助于理解性别差异。进一步的基因研究可实现对糜烂性食管炎高风险的预测并开发新的治疗方案。
