title: Regionally Smoothed Meta-Analysis Methods for GWAS Datasets.
abstract: Genome-wide association studies are proven tools for finding disease genes, but it is often necessary to combine many cohorts into a meta-analysis to detect statistically significant genetic effects. Often the component studies are performed by different investigators on different populations, using different chips with minimal SNPs overlap. In some cases, raw data are not available for imputation so that only the genotyped single nucleotide polymorphisms (SNPs) results can be used in meta-analysis. Even when SNP sets are comparable, different cohorts may have peak association signals at different SNPs within the same gene due to population differences in linkage disequilibrium or environmental interactions. We hypothesize that the power to detect statistical signals in these situations will improve by using a method that simultaneously meta-analyzes and smooths the signal over nearby markers. In this study, we propose regionally smoothed meta-analysis methods and compare their performance on real and simulated data.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Ferdouse
authors.initials: F
authors.lastname: Begum
authors.affiliation: Department of Information Science and Technology, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Monir H
authors.initials: MH
authors.lastname: Sharker
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: George C
authors.initials: GC
authors.lastname: Tseng
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
mesh_terms: D003198:Computer Simulation; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
keywords: GWAS meta-analysis; simulation; sliding-window; window-based method