On combining data from genome-wide association studies to discover disease-associated SNPs

DOI10.1214/09-STS286zbMATH Open1329.62434arXiv1010.5046OpenAlexW2092706317MaRDI QIDQ908136FDOQ908136

Authors: Ruth M. Pfeiffer, Mitchell H. Gail, David Pee 

Publication date: 3 February 2016

Published in: Statistical Science (Search for Journal in Brave)

Abstract: Combining data from several case-control genome-wide association (GWA) studies can yield greater efficiency for detecting associations of disease with single nucleotide polymorphisms (SNPs) than separate analyses of the component studies. We compared several procedures to combine GWA study data both in terms of the power to detect a disease-associated SNP while controlling the genome-wide significance level, and in terms of the detection probability ($mathitDP$). The $mathitDP$ is the probability that a particular disease-associated SNP will be among the $T$ most promising SNPs selected on the basis of low $p$-values. We studied both fixed effects and random effects models in which associations varied across studies. In settings of practical relevance, meta-analytic approaches that focus on a single degree of freedom had higher power and $mathitDP$ than global tests such as summing chi-square test-statistics across studies, Fisher's combination of $p$-values, and forming a combined list of the best SNPs from within each study.

Full work available at URL: https://arxiv.org/abs/1010.5046

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zbMATH Keywords

hypothesis testingrandom effectsWald testmultiple comparisonwhole genome scans

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Genetics and epigenetics (92D10) Paired and multiple comparisons; multiple testing (62J15)

Cites Work

• Genomic Control for Association Studies
• From Genotypes to Genes: Doubling the Sample Size
• A systematic comparison of methods for combining \(p\)-values from independent tests
• Valid Inference in Random Effects Meta‐Analysis
• Probability of detecting disease-associated single nucleotide polymorphisms in case-control genome-wide association studies

Cited In (14)

• Joint analysis of SNP and gene expression data in genetic association studies of complex diseases
• Probability of detecting disease-associated single nucleotide polymorphisms in case-control genome-wide association studies
• SHARE: an adaptive algorithm to select the most informative set of SNPs for candidate genetic association
• On combining family based and population based case-control data in association studies
• Generating SNP barcode to evaluate SNP-SNP interaction of disease by particle swarm opti\-mi\-zation
• Robust tests in genome-wide scans under incomplete linkage disequilibrium
• Modeling the Association Between Clusters of SNPs and Disease Responses
• Replicability analysis for genome-wide association studies
• A novel random effect model for GWAS meta-analysis and its application to trans-ethnic meta-analysis
• Methodological issues in multistage genome-wide association studies
• Meta-analysis and Combining Information in Genetics and Genomics
• Association tests through combining \(p\)-values for case control genome-wide association studies
• Collapsing SNP genotypes in case-control genome-wide association studies increases the type I error rate and power
• Dealing with heterogeneity between cohorts in genomewide SNP association studies

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