Table_2_Genome-Wide Epistatic Interaction Networks Affecting Feed Efficiency in Duroc and Landrace Pigs.xlsx

Interactions among genomic loci have often been overlooked in genome-wide association studies, revealing the combinatorial effects of variants on phenotype or disease manifestation. Unexplained genetic variance, interactions among causal genes of small effects, and biological pathways could be identified using a network biology approach. The main objective of this study was to determine the genome-wide epistatic variants affecting feed efficiency traits [feed conversion ratio (FCR) and residual feed intake (RFI)] based on weighted interaction SNP hub (WISH-R) method. Herein, we detected highly interconnected epistatic SNP modules, pathways, and potential biomarkers for the FCR and RFI in Duroc and Landrace purebreds considering the whole population, and separately for low and high feed efficient groups. Highly interacting SNP modules in Duroc (1,247 SNPs) and Landrace (1,215 SNPs) across the population and for low feed efficient (Duroc—80 SNPs, Landrace—146 SNPs) and high feed efficient group (Duroc—198 SNPs, Landrace—232 SNPs) for FCR and RFI were identified. Gene and pathway analyses identified ABL1, MAP3K4, MAP3K5, SEMA6A, KITLG, and KAT2B from chromosomes 1, 2, 5, and 13 underlying ErbB, Ras, Rap1, thyroid hormone, axon guidance pathways in Duroc. GABBR2, GNA12, and PRKCG genes from chromosomes 1, 3, and 6 pointed towards thyroid hormone, cGMP-PKG and cAMP pathways in Landrace. From Duroc low feed efficient group, the TPK1 gene was found involved with thiamine metabolism, whereas PARD6G, DLG2, CRB1 were involved with the hippo signaling pathway in high feed efficient group. PLOD1 and SETD7 genes were involved with lysine degradation in low feed efficient group in Landrace, while high feed efficient group pointed to genes underpinning valine, leucine, isoleucine degradation, and fatty acid elongation. Some SNPs and genes identified are known for their association with feed efficiency, others are novel and potentially provide new avenues for further research. Further validation of epistatic SNPs and genes identified here in a larger cohort would help to establish a framework for modelling epistatic variance in future methods of genomic prediction, increasing the accuracy of estimated genetic merit for FE and helping the pig breeding industry.

全基因组关联研究（Genome-Wide Association Study, GWAS）往往忽视了基因组位点间的互作，而这类互作恰恰能够揭示变异对表型或疾病发生的组合效应。采用网络生物学（network biology）方法，可识别未被解释的遗传方差、小效应致病基因间的互作以及生物学通路。本研究旨在基于加权互作单核苷酸多态性（Single Nucleotide Polymorphism, SNP）枢纽（WISH-R）法，鉴定影响饲料效率性状[饲料转化率（Feed Conversion Ratio, FCR）与剩余采食量（Residual Feed Intake, RFI）]的全基因组上位性变异。本研究以杜洛克（Duroc）与长白（Landrace）纯种猪为研究对象，分别针对全群体、低饲料效率组与高饲料效率组，鉴定得到与FCR及RFI相关的高度互联上位性SNP模块、生物学通路及潜在生物标志物。针对全群体的杜洛克猪（含1247个SNP）与长白猪（含1215个SNP），以及低饲料效率组（杜洛克猪80个SNP、长白猪146个SNP）与高饲料效率组（杜洛克猪198个SNP、长白猪232个SNP），本研究均鉴定出与FCR和RFI相关的高度互作SNP模块。基因与通路分析显示，杜洛克猪中位于1、2、5、13号染色体上的ABL1、MAP3K4、MAP3K5、SEMA6A、KITLG及KAT2B基因，分别参与调控ErbB、Ras、Rap1、甲状腺激素及轴突导向通路。长白猪中位于1、3、6号染色体上的GABBR2、GNA12及PRKCG基因，则与甲状腺激素、cGMP-PKG及cAMP通路相关。在杜洛克猪低饲料效率组中，TPK1基因参与硫胺素代谢通路；而在高饲料效率组中，PARD6G、DLG2及CRB1基因参与Hippo信号通路（Hippo signaling pathway）。长白猪低饲料效率组中的PLOD1与SETD7基因参与赖氨酸降解通路；而高饲料效率组的相关基因则参与缬氨酸、亮氨酸、异亮氨酸降解及脂肪酸延伸通路。本研究鉴定出的部分SNP与基因已被证实与饲料效率性状相关，其余则为全新发现，可为后续研究提供新的方向。在更大规模的队列中对本研究鉴定出的上位性SNP与基因进行进一步验证，将有助于建立用于未来基因组预测方法中上位性变异建模的框架，提升饲料效率（Feed Efficiency, FE）遗传评估值的准确性，进而推动猪育种产业的发展。