Genetic association study identifies genetic variants for non-alcoholic fatty liver without comorbidities in the...

Non-alcoholic fatty liver (NAFL) refers to a disease in which fat builds up in the liver, similar to what occurs for those who drink a lot of alcohol, even in cases of not drinking alcohol at all or only in a small amount. Along with non-alcoholic steatohepatitis (NASH), NAFL is a type of non-alcoholic fatty liver disease (NAFLD). Currently, the prevalence of NAFLD is increasing worldwide. A wide range of comorbidities that can increase the risk of NAFLD includes obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome.

This study aimed to discover genetic variants for NAFL in the Korean population.

Differing from previous studies, we conducted a genome-wide association study for NAFL in the selected subjects without comorbidities to rule out bias due to the inclusion of confounding effects of comorbidities. We grouped 424 NAFL cases and 5,402 controls from the Korean Genome and Epidemiology Study (KoGES) subjects without comorbidities such as dyslipidemia, type 2 diabetes, and metabolic syndrome. All subjects including cases and controls did not consume alcohol at all, or consumed less than 20 g/day for men and less than 10 g/day for women.

The logistic association analysis adjusting for sex, age, BMI, and waist circumference identified one novel genome-wide significant variant (rs7996045, P = 2.3 × 10^-8) for NAFL. This variant was located in the intron of CLDN10 and was not detected using previous conventional approaches in which confounding effects resulting from comorbidities were not considered in the study design stage. In addition, we detected several genetic variants showing suggestive association for NAFL (P < 10^-5).

The unique strategy in our association analysis of excluding major confounding factors provides, for the first time, an insight into the genuine genetic basis influencing NAFL.