title: Recent developments in genome and exome-wide analyses of plasma lipids.
abstract: OBJECTIVE
  Genome-wide association scans (GWAS) have identified over 100 human loci associated with variation in lipids. The identification of novel genes and variants that affect lipid levels is made possible by next-generation sequencing, rare variant discovery and analytic advances. The current status of the genetic basis of lipid traits will be presented.
  
  
  RESULTS
  Expansion of GWAS sample sizes for lipid traits has not substantially increased the proportion of trait variance explained by common genetic variants (less than 15% of trait variation captured). Although GWAS has discovered novel loci and pathways with putative biological function and impact on cardiovascular disease risk, discovery of the genes in these loci remains challenging. Exome sequencing promises to identify genes with protein-coding variants with a large impact on lipids, as shown for LDL-cholesterol levels associated with novel (PNPLA5) and known (LDLR, PCSK9, APOB) genes.
  
  
  CONCLUSIONS
  Current results have increased our understanding of the genetic architecture of lipids, expanding the range of effect and frequency for variants identified for lipid traits. Identification of novel lipid-associated gene variants, even if small in effect or rare in the population, could provide important novel drug targets and biological pathways for dyslipidemia.
authors.affiliation: aUniversity of North Carolina, Chapel Hill, North Carolina bUniversity of Michigan, Ann Arbor, Michigan cUniversity of Virginia, Charlottesville, Virginia, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Cristen J
authors.initials: CJ
authors.lastname: Willer
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
mesh_terms: D000818:Animals; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D059472:Exome; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D058990:Molecular Targeted Therapy; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids