Genetics of lipid traits: Genome-wide approaches yield new biology and clues to causality in coronary artery disease

• Genome-wide association studies have uncovered many novel gene influencing lipids.
• Identifying causal genes at new loci is difficult as many loci harbor multiple genes.
• Somatic gene manipulation and eQTL analyses have helped pinpoint causal genes.
• Exome array genotyping and sequencing are currently revealing functional variants.

A wealth of novel lipid loci have been identified through a variety of approaches focused on common and low-frequency variation and collaborative metaanalyses in multiethnic populations. Despite progress in identification of loci, the task of determining causal variants remains challenging. This work will undoubtedly be enhanced by improved understanding of regulatory DNA at a genomewide level as well as new methodologies for interrogating the relationships between noncoding SNPs and regulatory regions. Equally challenging is the identification of causal genes at novel loci. Some progress has been made for a handful of genes and comprehensive testing of candidate genes using multiple model systems is underway. Additional insights will be gleaned from focusing on low frequency and rare coding variation at candidate loci in large populations. This article is part of a Special Issue entitled: From Genome to Function.