PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism.

RECENT FINDINGS: The genetic loci for ATP-binding cassette transporters G5 and G8, Niemann-Pick C1-Like protein 1, sortilin-1, ABO blood-group glycosyltransferases, myosin regulatory light chain-interacting protein and cholesterol 7α-hydroxylase have all consistently been associated with LDL cholesterol levels and/or coronary artery disease in GWAS. Whole-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health.

SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol. Novel genes in LDL metabolism will improve our understanding of mechanisms in LDL metabolism, and may lead to the identification of new drug targets to reduce LDL cholesterol levels.