Abstract
BackgroundSeveral 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.MethodsWe 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.ResultsThe 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).ConclusionsThis 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.
Highlights
Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD)
We aimed to evaluate the longitudinal association between NAFLD and single-nucleotide polymorphism (SNP) in the Korean population
The validation set had a larger proportion of males and higher systolic and diastolic blood pressure, body mass index (BMI), also evaluated transaminase (ALT), total cholesterol and fasting glucose (p < 0.05)
Summary
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. Previous genome-wide association studies (GWASs) have identified a variety of genes and single-nucleotide polymorphisms (SNPs) that confer susceptibility to NAFLD [8]. Chung et al BMC Gastroenterology (2020) 20:344 variant at protein position 148 (I148M), on chromosome 22 was strongly associated with an increased liver fat content [9]. A systematic review showed that the rs738409 GG genotype was associated with liver fat accumulation and susceptibility to more aggressive disease traits in multiple ethnic groups [10]. In studies based on Asian populations, there were significant associations of PNPLA3 with the occurrence and severity of NAFLD [11,12,13]
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