Department of Internal Medicine, Gangnam Healthcare Center, Seoul National University Hospital, 39FL., Gangnam Finance center 737, Yeoksam-Dong, Gangnam-Gu, Seoul, 135-984, South Korea.
DNA Link, Inc., Seoul, South Korea.
BMC Gastroenterol. 2020 Oct 15;20(1):344. doi: 10.1186/s12876-020-01469-8.
Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD.
We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes.
The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531).
This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.
已知几种遗传变异与非酒精性脂肪性肝病（NAFLD）相关。我们旨在评估遗传变异与 NAFLD 之间的纵向关联。
我们对接受重复健康检查的韩国个体进行了全基因组关联研究（GWAS）。NAFLD 通过超声检查和排除继发性病因来定义。
研究对象的中位年龄为 50.0 岁，其中 54.8%为男性。中位随访时间为 39 个月。在基线时无 NAFLD 的 3905 名受试者中，874 名（22.4%）受试者发生了 NAFLD，而在基线时有 NAFLD 的 1818 名受试者中，336 名（18.5%）受试者在随访期间 NAFLD 消退。在调整年龄、性别和体重指数后，没有单个核苷酸多态性（SNP）在 NAFLD 的发生或消退中通过全基因组显著的 Bonferroni 校正。在 GWAS 中的发现集 SNP 中，仅 1 个 SNP（rs4906353）与 NAFLD 的发生具有相关性，在验证集中具有边缘显著性（发现集 p 值=9.68E-5，验证集 p 值=0.00531）。
这项探索性研究表明，NAFLD 的纵向变化与韩国人群中的遗传变异无关。这些发现为 NAFLD 发病机制中的遗传机制提供了新的见解。
