Genomic Convergence of Genome-wide Investigations for Complex Traits
Date
2009Sujet
Résumé
Genome-wide investigations for identifying the genes for complex traits are considered to be agnostic in terms of prior assumptions for the responsible DNA alterations. The agreement of genome-wide association studies (GWAS) and genome-wide linkage scans (GWLS) has not been explored to date. In this study, a genomic convergence approach of GWAS and GWLS was implemented for the first time in order to identify genomic loci supported by both methods. A database with 376 GWLS and 102 GWAS for 19 complex traits was created. Data regarding the location and statistical significance for each genetic marker were extracted from articles or web-based databases. Convergence was quantified as the proportion of significant GWAS markers located within linked regions. Convergence was variable (0-73.3%) and was found to be significantly higher than expected by chance only for two of the 19 phenotypes. Seventy five loci of interest were identified, which being supported by independent lines of evidence, could merit prioritization in future investigations. Although convergence is supportive of genuine effects, lack of agreement between GWLS and GWAS is also indicative that these studies are designed to answer different questions and are not equally well suited for deciphering the genetics of complex traits.
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