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Population-specific genotype imputations using minimac or IMPUTE2
Elisabeth M van Leeuwen1, Alexandros Kanterakis2, Patrick Deelen2
1Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Nature Protocols
|July 31, 2015
Summary
Combining genome-wide association studies (GWASs) requires consistent single-nucleotide polymorphisms (SNPs). This protocol details imputation methods using minimac and IMPUTE2 for enhanced genetic variant analysis.
Area of Science:
- Genetics
- Bioinformatics
- Computational Biology
Background:
- Genome-wide association studies (GWASs) require large sample sizes for robust analysis of common and rare genetic variants.
- Meta-analysis of multiple cohorts increases statistical power but necessitates standardized genetic data, specifically identical single-nucleotide polymorphisms (SNPs).
- Genotype imputation is a crucial method for harmonizing SNP data across diverse cohorts when direct genotyping is incomplete.
Purpose of the Study:
- To provide comprehensive guidelines for performing genotype imputation using minimac and IMPUTE2.
- To detail the application of these imputation methods within the Genome of the Netherlands (GoNL) consortium.
- To identify factors influencing the quality of genetic imputation.
Main Methods:
- The protocol outlines genotype imputation procedures using the minimac and IMPUTE2 software.
- It incorporates the use of a population-specific reference panel developed by the Genome of the Netherlands (GoNL) consortium.
- Guidelines are provided for imputing genotypes in large biobanks.
Main Results:
- The protocol has been successfully applied by the Genome of the Netherlands (GoNL) consortium for imputing genetic data in Dutch biobanks.
- The developed guidelines facilitate the harmonization of SNP data across different cohorts for meta-analysis.
- Factors affecting imputation quality are discussed to optimize results.
Conclusions:
- This protocol offers a standardized approach for genotype imputation, essential for powerful GWAS meta-analyses.
- The use of population-specific reference panels, like the one from GoNL, enhances imputation accuracy.
- The guidelines are practical for large-scale biobank imputation projects, requiring several days for completion.
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