摘要Objective This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease(NAFLD)in children with obesity.Methods We conducted a two-step case-control study.Ninety-three participants were subjected to whole-exome sequencing(exploratory set).Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing(validation set).Results In the exploratory set,14 genes from the NAFLD-associated pathways were identified.In the validation set,after adjusting for sex,age,and body mass index,ECI2 rs2326408(dominant model:OR=1.33,95%CI:1.02-1.72;additive model:OR=1.22,95%CI:1.01-1.47),C6orf201 rs659305(dominant model:OR=1.30,95%CI:1.01-1.69;additive model:OR=1.21,95%CI:1.00-1.45),CALML5 rs10904516(pre-ad dominant model:OR=1.36,95%CI:1.01-1.83;adjusted dominant model:OR=1.40,95%CI:1.03-1.91;and pre-ad additive model:OR=1.26,95%CI:1.04-1.66)polymorphisms were significantly associated with NAFLD in children with obesity(P<0.05).Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516,COX11 rs17209882,and SCD5 rs3733228 was optional(P<0.05),demonstrating a negative interaction between the three genes.Conclusion In the Chinese population,the CALML5 rs10904516,C6orf201 rs659305,and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.