title: Sequential sentinel SNP Regional Association Plots (SSS-RAP): an approach for testing independence of SNP association signals using meta-analysis data.
abstract: Genome-Wide Association Studies (GWAS) frequently incorporate meta-analysis within their framework. However, conditional analysis of individual-level data, which is an established approach for fine mapping of causal sites, is often precluded where only group-level summary data are available for analysis. Here, we present a numerical and graphical approach, "sequential sentinel SNP regional association plot" (SSS-RAP), which estimates regression coefficients (beta) with their standard errors using the meta-analysis summary results directly. Under an additive model, typical for genes with small effect, the effect for a sentinel SNP can be transformed to the predicted effect for a possibly dependent SNP through a 2×2 2-SNP haplotypes table. The approach assumes Hardy-Weinberg equilibrium for test SNPs. SSS-RAP is available as a Web-tool (http://apps.biocompute.org.uk/sssrap/sssrap.cgi). To develop and illustrate SSS-RAP we analyzed lipid and ECG traits data from the British Women's Heart and Health Study (BWHHS), evaluated a meta-analysis for ECG trait and presented several simulations. We compared results with existing approaches such as model selection methods and conditional analysis. Generally findings were consistent. SSS-RAP represents a tool for testing independence of SNP association signals using meta-analysis data, and is also a convenient approach based on biological principles for fine mapping in group level summary data.
authors.affiliation: Bristol Genetic Epidemiology Laboratories, Department of Social Medicine, University of Bristol, Bristol, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Tom R
authors.initials: TR
authors.lastname: Gaunt
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D004562:Electrocardiography; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000032:analysis; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis
chemical_list: D008055:Lipids