A GWAS Study on Liver Function Test Using eMERGE Network Participants.

Liver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations.The process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously. After removing missing data and outliers based on principal components (PC) analyses, 3294 samples from European ancestry were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and total serum bilirubin and other liver function tests was tested using linear regression, adjusting for age, gender, site, platform and ancestry principal components (PC).Consistent with previous results, a strong association signal has been detected for UGT1A gene cluster (best SNP rs887829, beta = 0.15, p = 1.30x10-118) for total serum bilirubin level. Indeed, in this region more than 176 SNPs (or indels) had p