A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10^-09; rs12008279—OR 1.56, P = 1.53 x 10^-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10^-09; rs6622126—OR 1.75, P = 4.04x10^-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10^-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10^-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

Improving feed efficiency (FE) is a major goal of pig breeding, reducing production costs and providing sustainability to the pig industry. Reliable predictors for FE could assist pig producers. We carried out untargeted blood metabolite profiling in uncastrated males from Danbred Duroc (n = 59) and Danbred Landrace (n = 50) pigs at the beginning and end of a FE testing phase to identify biomarkers and biological processes underlying FE and related traits. By applying linear modeling and clustering analyses coupled with WGCNA framework, we identified 102 and 73 relevant metabolites in Duroc and Landrace based on two sampling time points. Among them, choline and pyridoxamine were hub metabolites in Duroc in early testing phase, while, acetoacetate, cholesterol sulfate, xanthine, and deoxyuridine were identified in the end of testing. In Landrace, cholesterol sulfate, thiamine, L-methionine, chenodeoxycholate were identified at early testing phase, while, D-glutamate, pyridoxamine, deoxycytidine, and L-2-aminoadipate were found at the end of testing. Validation of these results in larger populations could establish FE prediction using metabolomics biomarkers. We conclude that it is possible to identify a link between blood metabolite profiles and FE. These results could lead to improved nutrient utilization, reduced production costs, and increased FE.

Meat quality is a complex trait that is influenced by genetic and environmental factors, which includes mineral concentration. However, the association between mineral concentration and meat quality, and the specific molecular pathways underlying this association, are not well explored. We therefore analyzed gene expression as measured with RNA-seq in Longissimus thoracis muscle of 194 Nelore steers for association with three meat quality traits (intramuscular fat, meat pH, and tenderness) and the concentration of 13 minerals (Ca, Cr, Co, Cu, Fe, K, Mg, Mn, Na, P, S, Se, and Zn). We identified seven sets of co-expressed genes (modules) associated with at least two traits, which indicates that common pathways influence these traits. From pathway analysis of module hub genes, we further found an over-representation for energy and protein metabolism (AMPK and mTOR signaling pathways) in addition to muscle growth, and protein turnover pathways. Among the identified hub genes FASN, ELOV5, and PDE3B are involved with lipid metabolism and were affected by previously identified eQTLs associated to fat deposition. The reported hub genes and over-represented pathways provide evidence of interplay among gene expression, mineral concentration, and meat quality traits. Future studies investigating the effect of different levels of mineral supplementation in the gene expression and meat quality traits could help us to elucidate the regulatory mechanism by which the genes/pathways are affected.

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 amongst 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.