Genome-wide association and Mendelian randomization analyses of placental efficiency and piglet birth weight in Danish Large White pigs.

Abstract

Objective: Modern swine breeding has been shifted from maximizing productivity to improving quality for better efficiency. A key goal is to balance litter size with piglet birth weight (BW). This study focused on Danish Large White pigs to evaluate a novel placental efficiency (PEA) index based on placental area (PA) as a biologically relevant and measurable trait for breeding programs.

Methods: The study integrated genome-wide association studies and Mendelian randomization to explore the genetic relationship and potential causal direction between the proposed PEA index and piglet BW. The investigation used data from 113 piglets.

Results: Analysis revealed a significant positive causal effect of PEA on BW. Nine significant single nucleotide polymorphisms and eight candidate genes (MARVELD3, CMTR2, TLE7, CHST4, TAT, ZNF23, CALB2, PHLPP2) were identified. Functional enrichment analysis indicated that these genes synergistically regulate placental function: TAT is involved in amino acid metabolism and energy homeostasis; CALB2 may influence trophoblast signaling and placental vascular function via calcium regulation; CHST4 participates in extracellular matrix modification at the maternal-fetal interface; MARVELD3 contributes to placental barrier maintenance; CMTR2 and TLE7 are involved in RNA modification and transcriptional regulation; ZNF23 may regulate cell cycle and differentiation; and PHLPP2 influences cell survival and metabolic adaptation via AKT signaling. These network regulates placental endothelial activity, optimizes nutrient allocation, and positively impacts BW.

Conclusion: This study clarifies, from a genetic perspective, the causal relationship between PEA and BW. The proposed PEA index is presented as a reliable tool for evaluating placental spatial utilization efficiency in polytocous animal breeding. It offers new genetic insights and a potential approach for improving litter viability.