Insights into blood lipids from rare variant discovery

Large-scale genome wide screens have discovered over 160 common variants associated with plasma lipids, which are risk factors often linked to heart disease. A large fraction of lipid heritability remains unexplained, and it is hypothesized that rare variants of functional consequence may account for some of the missing heritability. Finding lipid-associated variants that occur less frequently in the human population poses a challenge, primarily due to lack of power and difficulties to identify and test them. Interrogation of the protein-coding regions of the genome using array and sequencing techniques has led to important discoveries of rare variants that affect lipid levels and related disease risk. Here, we summarize the latest methods and findings that contribute to our current understanding of rare variant lipid genetics.