Defining the spectrum of alleles that contribute to blood lipid concentrations in humans.
OBJECTIVE
Recently, genome-wide genetic screening of common DNA sequence variants has proven a successful approach to identify novel genetic contributors to complex traits. This review summarizes recent genome-wide association studies for lipid phenotypes, and evaluates the next steps needed to obtain a full picture of genotype-phenotype correlation and apply these findings to inform clinical practice.


RESULTS
So far, genome-wide association studies have defined at least 19 genomic regions that contain common DNA single nucleotide polymorphisms associated with LDL cholesterol, HDL cholesterol and/or triglycerides. Of these, eight represent novel loci in humans, whereas 11 genes have been previously implicated in lipoprotein metabolism. Many of the same loci with common variants have already been shown to lead to monogenic lipid disorders in humans and/or mice, suggesting that a spectrum of common and rare alleles at each validated locus contributes to blood lipid concentrations.


CONCLUSIONS
At least 19 loci harbor common variations that contribute to blood lipid concentrations in humans. Larger scale genome-wide association studies should identify additional loci, and sequencing of these loci should pinpoint all relevant alleles. With a full catalog of DNA polymorphisms in hand, a panel of lipid-related variants can be studied to provide clinical risk stratification and targeting of therapeutic interventions.
Kathiresan
Sekar
S
Cardiovascular Disease Prevention Center, Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. skathiresan@partners.org
Musunuru
Kiran
K
Orho-Melander
Marju
M
D000483:Alleles; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000235:genetics*
D008055:Lipids