Haplotype Analysis Improved Evidence for Candidate Genes for Intramuscular Fat Percentage from a Genome Wide Association Study of Cattle

Abstract

In genome wide association studies (GWAS), haplotype analyses of SNP data are neglected in favour of single point analysis of associations. In a recent GWAS, we found that none of the known candidate genes for intramuscular fat (IMF) had been identified. In this study, data from the GWAS for these candidate genes were re-analysed as haplotypes. First, we confirmed that the methodology would find evidence for association between haplotypes in candidate genes of the calpain-calpastatin complex and musculus longissimus lumborum peak force (LLPF), because these genes had been confirmed through single point analysis in the GWAS. Then, for intramuscular fat percent (IMF), we found significant partial haplotype substitution effects for the genes ADIPOQ and CXCR4, as well as suggestive associations to the genes CEBPA, FASN, and CAPN1. Haplotypes for these genes explained 80% more of the phenotypic variance compared to the best single SNP. For some genes the analyses suggested that there was more than one causative mutation in some genes, or confirmed that some causative mutations are limited to particular subgroups of a species. Fitting the SNPs and their interactions simultaneously explained a similar amount of the phenotypic variance compared to haplotype analyses. Haplotype analysis is a neglected part of the suite of tools used to analyse GWAS data, would be a useful method to extract more information from these data sets, and may contribute to reducing the missing heritability problem.