Using haplotype probabilities in categorical survival analysis: a case study with three candidate genes in an Iberian × Meishan F₂ population of newborn piglets

Abstract

Haplotype probabilities have been implemented in association analyses performed between three candidate genes and the preweaning survival of F2 Iberian x Meishan piglets, under a categorical proportional hazard model. The additive effect of substitution of each haplotype was estimated using information of parental genotypes for non-genotyped piglets. Analysed loci were the bone morphogenetic protein type 1B receptor (BMPR1B) gene at 8q25 (three SNPs; haplotypes BMPR1B A, BMPR1B B, BMPR1B C and BMPR1B D), the dopamine beta-hydroxylase (DBH) gene at 1q2.13 (two SNPs; haplotypes DBH X, DBH Y and DBH Z), and the prolactin receptor (PRLR) gene at 16q1.4-q2.3 (six SNPs; haplotypes PRLR A, PRLR B, PRLR C, PRLR D and PRLR E). The number of analysed records were 899 (BMPR1B), 850 (DBH) and 822 (PRLR) with a censoring percentage ranged between 87 and 89%. Associations with preweaning survival were suggested for BMPR1B (p < 0.10) and associations were clearly significant for DBH haplotypes (p < 0.05), whereas the PRLR locus did not reach statistical significance (p > 0.10). The BMPR1B A haplotype could increase piglet survivability in relation to the BMPR1B B haplotype with a hazard ratio of 0.751 and a confidence interval (CI) between 0.550 and 1.025 (p < 0.10). The two remaining haplotypes did not differ significantly from the BMPR1B B haplotype, with a hazard ratio higher than 0.90 (p > 0.10). For the DBH locus, the DBH X and the DBH Z haplotypes were associated with an improved preweaning survival in relation to the DBH Y haplotype. The advantage for DBH X in terms of hazard ratio was 0.789 (CI = 0.625 to 0.994; p < 0.05) and differences between DBH Y and DBH Z reached a hazard ratio of 0.770 (CI = 0.606 to 0.977; p < 0.05). Although further researches are required, BMPR1B and DBH genes could be a useful tool to improve piglet survival under a marker assisted selection strategy.