Functional genomic analysis reveals HAVCR1 as the key regulator of 5q33.3 locus linked to hyperlipidemia

Given the high heritability of lipid traits, genome-wide association studies (GWAS) have identified numerous loci associated with serum lipids; however, pinpointing the causal variants remains a challenge.

Here, we investigated the 5q33.3 locus and identified HAVCR1 as a likely effector gene influencing lipid metabolism. By integrating functional genomics and experimental validation, we identified two non-linked variants, rs6882076 and rs17573010, that modulate HAVCR1 via allele-specific binding by IRF2 and GATA4, respectively. rs6882076 was refined from prior GWAS findings, while rs17573010 emerged from ancestry-specific analysis.