Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in children with an estimated prevalence of 9%. Children with NAFLD are at increased risk for both hepatic and non-hepatic morbidity and mortality. NAFLD comprises a spectrum with only some individuals developing a more advanced form, nonalcoholic steatohepatitis (NASH). NAFLD is associated with cirrhosis in some children; however, a standard definition for NASH in children is lacking.

Genetics of Pediatric Nonalcoholic Fatty Liver Disease is a study of the NIH NASH CRN. DNA was collected from the parents of pediatric patients in the IRB approved studies: TONIC (Treatment of Nonalcoholic fatty liver disease in Children) and NASH CRN Registry. The NASH CRN consists of 10 academic sites nationwide, focused on determining the cause of, as well as finding a treatment for, NAFLD in children and adults. The network is sponsored by the NIDDK and NICHD and supported by NCI to collect information on the etiology, contributing factors, natural history, complications, and therapy of NAFLD.

All children and their parents with a DNA sample were genotyped and analyzed. Initially, a candidate gene approach was used, testing SNPs in pathways for adipose regulation and carbohydrate and lipid metabolism.

To investigate candidate alleles that may influence NASH susceptibility by genotyping DNA samples from children with NAFLD and their parents.

All children (under age 18 and meeting each NASH CRN study-specific enrollment and exclusion criteria) enrolled in any NASH CRN study (NALFD Database, NAFLD Pediatric Database 2, TONIC, CyNCh) at a participating site with IRB approval for the GOALS study and each of their available biological parents who consent to participating in the GOALS study. Each parent provides a blood specimen for DNA extraction and completes a survey reporting basic self-reported demographic and medical history.

Plans are to proceed to a whole genome approach once funds are secured. The trios will be analyzed using Transmission Disequilibrium Test (TDT) analysis with a suite of software applications to perform genetic association analyses in nuclear families as well as unrelated subjects.