PNPLA3I148M was associated with altered hepatic levels of metabolic dysfunction–associated steatotic liver disease (MASLD)‐associated and cholesterol synthesis–associated transcripts. Liver biopsy homogenates from individuals without known liver disease were analyzed using human transcriptome array and grouped by genotype for the PNPLA3I148M. (a and b) Transcript levels of MASLD associated genes patatin‐like phospholipase domain containing 3(PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), glucokinase regulator (GCKR), and membrane bound O‐acyltransferase domain containing 7 (MBOAT7) (c) Transcript levels of cholesterol synthesis associated genes, in patients without statin therapy, 3‐hydroxy‐3‐methylglutaryl‐CoA synthase (HMGCS), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) and (d) SREBF2. 148II—homozygote for the enzymatically active allele, 148I/M—heterozygote, and 148MM—homozygote for the enzymatically inactive alleles. Data are expressed as min to max box plots with middle line at median, each dot represents one patient. One‐way ANOVA, Fisher's least significant difference (LSD) test. n.s., not significant. *p < 0.05 and **p < 0.01 (n = 15–83/group).