期刊
GENOMICS
卷 92, 期 5, 页码 265-272出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2008.07.011
关键词
Pathway; Genome-wide; Disease; Common; Diabetes; Crohn's; Coronary; Bipolar; Arthritis; Hypertension
资金
- National Heart Lung
- Blood Institute [U01 HL064777-06]
- National Institute on Aging Longevity Consortium [U19 AG023122-01]
- NIMH [1 R01 MH078151-01A1]
- National Institutes of Health [N01 MH22005, U01 DA024417-01, P50 MH081755-01]
- NIH [1 U54 RR025204-01]
Recent genome-wide association studies (GWAS) have identified DNA sequence variations that exhibit unequivocal statistical associations with many common chronic diseases. However, the vast majority of these studies identified variations that explain only a very small fraction of disease burden in the population at large, suggesting that other factors, such as multiple rare or low-penetrance variations and interacting environmental factors, are major contributors to disease susceptibility. Identifying multiple low-penetrance variations (or polygenes) contributing to disease susceptibility will be difficult. We present a pathway analysis approach to characterizing the likely polygenic basis of seven common diseases using the Wellcome Trust Case Control Consortium (WTCCC) GWAS results. We identify numerous pathways implicated in disease predisposition that would have not been revealed using standard single-locus GWAS statistical analysis criteria. Many of these pathways have long been assumed to contain polymorphic genes that lead to disease predisposition. Additionally, we analyze the genetic relationships between the seven diseases, and based upon similarities with respect to the associated genes and pathways affected in each, propose a new way of categorizing the diseases. (C) 2008 Elsevier Inc. All rights reserved.
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