Using Imputed Genotypes for Relative Risk Estimation in Case-Parent Studies

摘要

Meta-analyses of genome-wide association studies are often based on imputed single nucleotide polymorphismn(SNP) data, because component studies were genotyped using different platforms. One would like to include case-nparent triad studies along with case-control studies in suchmeta-analyses. However, there are no publishedmethodsnfor estimating relative risks from imputed data for case-parent triad studies. The authors propose a method fornestimating the relative risk for a variant SNP allele based on a log-additive model. Their simulations first confirm thatnthe proposed method performs well with genotyped SNP data. As an empirical test of the method’s behavior withnimputed SNPs, the authors then apply it to chromosome 22 data fromtheMexicoCityChildhoodAsthmaStudy (1998–n2003). For chromosome 22, the authors had data on 7,293 SNPs that were both genotyped and imputed using thensoftwareMACH,which relies on linkage disequilibriumwith nearbySNPs.Correlation between estimated relative risksnbased on the actual genotypes and those based on the imputed genotypeswas remarkably high (rn2n¼0.95), validatingnthis method of relative risk estimation for the case-parent study design. This method should be useful to investigatorsnwho wish to conduct meta-analyses using imputed SNP data from both case-parent triad and case-control studies.