Mixture models are appealing for identifying hidden structures affecting somatic cell score (SCS) data, such as unrecorded cases of subclinical mastitis. Thus, liability-normal mixture (LNM) models were used for genetic analysis of SCS data, with the aim of predicting breeding values for such cases of mastitis. Here, putative mastitis statuses and breeding values for liability to putative mastitis were inferred solely from SCS observations. In total, there were 395,906 test-day records for SCS from 50,607 Danish Holstein cows. Four different statistical models were fitted: A) a classical (nonmixture) random regression model for test-day SCS; B1) an LNM test-day model assuming homogeneous (co)variance components for SCS from healthy (IMI-) and infected (IMI+) udders; B2) an LNM model identical to B1, but assuming heterogeneous residual variances for SCS from IMI- and IMI+ udders; and C) an LNM model assuming fully heterogeneous (co)variance components of SCS from IMI- and IMI+ udders. For the LNM models, parameters were estimated with Gibbs sampling. For model C, variance components for SCS were lower, and the corresponding heritabilities and repeatabilities were substantially greater for SCS from IMI- udders relative to SCS from IMI+ udders. Further, the genetic correlation between SCS of IMI- and SCS of IMI+ was 0.61, and heritability for liability to putative mastitis was 0.07. Models B2 and C allocated approximately 30% of SCS records to IMI+, but for model B1 this fraction was only 10%. The correlation between estimated breeding values for liability to putative mastitis based on the model (SCS for model A) and estimated breeding values for liability to clinical mastitis from the national evaluation was greatest for model B1, followed by models A, C, and B2. This may be explained by model B1 categorizing only the most extreme SCS observations as mastitic, and such cases of subclinical infections may be the most closely related to clinical (treated) mastitis.
BackgroundDespite many success stories of genome wide association studies (GWAS), challenges exist in QTL detection especially in datasets with many levels of relatedness. In this study we compared four methods of GWA on a dataset simulated for the 15th QTL-MAS workshop. The four methods were 1) Mixed model analysis (MMA), 2) Random haplotype model (RHM), 3) Genealogy-based mixed model (GENMIX), and 4) Bayesian variable selection (BVS). The data consisted of phenotypes of 2000 animals from 20 sire families and were genotyped with 9990 SNPs on five chromosomes.ResultsOut of the eight simulated QTL, these four methods MMA, RHM, GENMIX and BVS identified 6, 6, 8 and 7 QTL respectively and 4 QTL were common across the methods. GENMIX had the highest power to detect QTL however it also produced 4 false positives. BVS was the second best method in terms of power, detecting all QTL except the one on chromosome 5 with epistatic interaction. Two spurious associations were obtained across methods. Though all the methods considered the full pedigree in the analyses, it was not sufficient to avoid all the spurious associations arising due to family structure.ConclusionsUsing several methods with divergent approaches for GWAS can be useful in gaining confidence on the QTL identified. In our comparison, GENMIX was found to be the best method in terms of power but it needs appropriate correction for multiple testing to avoid the false positives. This study shows that the issues of multiple testing and the relatedness among study samples need special attention in GWAS.
The reaction norm model is becoming a popular approach to study genotype x environment interaction (GxE), especially when there is a continuum of environmental effects. These effects are typically unknown, and an approximation that is used in the literature is to replace them by the phenotypic means of each environment. It has been shown that this method results in poor inferences and that a more satisfactory alternative is to infer environmental effects jointly with the other parameters of the model. Such a reaction norm model with unknown covariates and heterogeneous residual variances across herds was fitted to milk, protein, and fat yield of first-lactation Danish Holstein cows to investigate the presence of GxE. Data included 188,502 first test-day records from 299 herds and 3,775 herd-years in a time period ranging from 1991 to 2003. Variance components and breeding values were estimated with a Bayesian approach implemented using Markov chain Monte Carlo. The posterior distribution of the variance of genetic slopes was markedly shifted away from zero for all traits under study, supporting the presence of GxE. The ratio of the genetic slope variance to the genetic level variance was highest for fat yield, followed by protein and milk yields. Genetic correlations between environments that differ by plus and minus 1 standard deviation from the mean environmental effect were 0.93, 0.91, and 0.89 for milk, protein, and fat yield, respectively. Genetic variances and heritabilities increased with increasing level of environmental effects. The rank correlations between predicted breeding values at the 5th and 95th percentiles of the distribution of environmental effects were, respectively, equal to 0.91, 0.90, and 0.76, for milk, protein, and fat yield. Thus in this study, although GxE was detected, it has a small effect on reranking of candidates for selection.
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