A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH.
A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (
Gawrieh, Samer; Guo, Xiuqing; Tan, Jingyi; Lauzon, Marie; Taylor, Kent D; Loomba, Rohit; Cummings, Oscar W; Pillai, Sreekumar; Bhatnagar, Pallav; Kowdley, Kris V; Yates, Katherine; Wilson, Laura A; Chen, Yii-Der Ida; Rotter, Jerome I; and Chalasani, Naga, "A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH." (2019). Articles, Abstracts, and Reports. 2585.