Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Curr Atheroscler Rep. 2012 Aug;14(4):295-9. doi: 10.1007/s11883-012-0245-0.

The enigma of genetics etiology of atherosclerosis in the post-GWAS era.

Author information

  • 1Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, 77030, USA. Ali.J.Marian@uth.tmc.edu

Abstract

Coronary atherosclerosis is a complex heritable trait with an enigmatic genetic etiology. Genome-wide association studies (GWAS) have successfully led to identification of over 100 different loci for susceptibility to coronary atherosclerosis. Most identified single nucleotide polymorphisms (SNP)s and genes have not been previously implicated in the pathogenesis of atherosclerosis and hence, have modest biological plausibility. The novel discoveries, however, might provide the opportunity for identification of new pathways and consequently novel preventive and therapeutic targets. A notable outcome of GWAS is relatively modest effect sizes of the associated SNPs. Collectively, the identified SNPs account for a relatively small fraction of heritability of coronary atherosclerosis, which raises the question of "missing heritability". Because GWAS test the common disease-comment variant hypothesis, a plausible explanation might be the presence of uncommon and rare variants in the genome that are untested in GWAS but that might exert large effect sizes on the risk of atherosclerosis. The latter, however, remains an empiric question pending validation through experimentation. Alternative mechanisms, such as transgenerational epigenetics including microRNAs, might in part account for the heritability of coronary atherosclerosis. Collectively, the recent findings are indicative of the etiological complexity of coronary atherosclerosis. Hence, it is expected that genetic etiology of coronary atherosclerosis will remain enigmatic in the foreseeable future.

PMID:
22437283
[PubMed - indexed for MEDLINE]
PMCID:
PMC3389254
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer Icon for PubMed Central
    Loading ...
    Write to the Help Desk