Journal Article

GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies

Li, Dawei, Sulovari, Arvis

2014

Overview

Background Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. Results In this study, we have developed a tool, GACT, which stands for G enome build and A llele definition C onversion T ool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate > 0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. Conclusion GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of genotypes from SNP-arrays or deep-sequencing, particularly for data from the dbGaP and other public databases. GACT software http://www.uvm.edu/genomics/software/gact

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Alleles / Animal Genetics and Genomics / Biomedical and Life Sciences / Datasets as Topic / Gene Frequency / Genes / Genetic aspects / Genetic Association Studies / Genome / Genomics / Genomics - methods / Genotype / Genotypes / Humans / Life Sciences / Methods / Microarrays / Microbial Genetics and Genomics / Plant Genetics and Genomics / Polymorphism, Single Nucleotide / Proteomics / Single nucleotide polymorphisms / Software / Transcriptomic methods