In the setting of genome-wide association studies, we propose a method for assigning a measure of significance to pre-defined sets of markers in the genome. The sets can be genes, conserved regions, or groups of genes such as pathways. Using the proposed methods and algorithms, evidence for association between a particular functional unit and a disease status can be obtained not just by the presence of a strong signal from a SNP within it, but also by the combination of several simultaneous weaker signals that are not strongly correlated. This approach has several advantages. First, moderately strong signals from different SNPs are combined to obtain a much stronger signal for the set, therefore increasing power. Second, in combination with methods that provide information on untyped markers, it leads to results that can be readily combined across studies and platforms that might use different SNPs. Third, the results are easy to interpret, since they refer to functional sets of markers that are likely to behave as a unit in their phenotypic effect. Finally, the availability of gene-level p-values for association is the first step in developing methods that integrate information from pathways and networks with genome-wide association data, and these can lead to a better understanding of the complex traits genetic architecture. The power of the approach is investigated in simulated and real datasets. Novel Crohn's disease associations are found using the WTCCC data.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.