Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen

Rare variants and blood LDL cholesterol A current goal in genomics is to identify genetic variation associated with actionable traits of clinical concern. Through exome sequencing of an Old Order Amish population, Montasser et al . identified a genetic variant that results in an amino acid change in the beta-1,4-galactosyltransferase 1 protein and is correlated with lower levels of cardiovascular disease. Investigation of the mutant protein showed that it affects genes associated with low-density lipoprotein cholesterol (LDL-C), and mice engineered to express the mutant protein exhibited a 38% decrease in blood LDL-C levels. This study suggests that such genomic sequencing and analysis can link genotype to phenotype and identify potentially clinically actionable pathways to treat disease. —LMZ