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PMID: 20813421 Published · ppublish English Journal Article

Towards a complete resolution of the genetic architecture of disease.

Trends in genetics : TIG ·Vol. 26 ·No. 10 ·2010-10-00 ·Pages 438-42

Singleton AB, Hardy J, Traynor BJ, Houlden H

Abstract

After years of linear gains in the genetic dissection of human disease we are now in a period of exponential discovery. This is particularly apparent for complex disease. Genome-wide association studies (GWAS) have provided myriad associations between common variability and disease, and have shown that common genetic variability is unlikely to explain the entire genetic predisposition to disease. Here we detail how one can expand on this success and systematically identify genetic risks that lead or predispose to disease using next-generation sequencing. Geneticists have had for many years a protocol to identify Mendelian disease. A similar set of tools is now available for the identification of rare moderate-risk loci and common low-risk variants. Whereas major challenges undoubtedly remain, particularly regarding data handling and the functional classification of variants, we suggest that these will be largely practical and not conceptual.

MeSH Terms
Alleles Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Humans Risk Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Singleton Andrew B
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. [email protected]
Hardy John
Traynor Bryan J
Houlden Henry
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Article Info
Journal
Trends in genetics : TIG
Abbr.
Trends Genet
ISSN
0168-9525
DOI
10.1016/j.tig.2010.07.004
Email
[email protected]
Published
2010-10-00
Pages
438-42
Language
English
Region
England
NLM ID
8507085
PMCID
PMC2943029
Subset
IM
Grants
Medical Research Council · G0601943 · United Kingdom
Medical Research Council · G0701075 · United Kingdom
Medical Research Council · G0802760 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.tig.2010.07.004 PMC Full Text View journal details
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