Abstract

Genome-wide association studies (GWASs) have enabled the discovery of common genetic variation contributing to normal and pathological traits and clinical drug responses, but recognizing the precise targets of these associations is now the major challenge. Here, we review recent approaches to the functional follow-up of GWAS loci, including fine mapping of GWAS signal(s), prioritization of putative functional SNPs by the integration of genetic epidemiological and bioinformatic methods, and in vitro and in vivo experimental verification of predicted molecular mechanisms for identifying the targeted genes. The majority of GWAS-identified variants fall in noncoding regions of the genome. Therefore, this review focuses on strategies for assessing likely mechanisms affected by noncoding variants; such mechanisms include transcriptional regulation, noncoding RNA function, and epigenetic regulation. These approaches have already accelerated progress from genetic studies to biological knowledge and might ultimately guide the development of prognostic, preventive, and therapeutic measures.

Authors	Edwards, Stacey L.; Beesley, Jonathan; French, Juliet D.; Dunning, Alison M.
Journal	AMERICAN JOURNAL OF HUMAN GENETICS
Pages	779-97
Volume	93
Date	1/11/2013
Grant ID	ECF-12-04
Funding Body	National Breast Cancer Foundation
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=doi: 10.1016/j.ajhg.2013.10.012.
	Download Article