387 Genome-wide association for chronic passive congestive livers associated with Bovine Congestive Heart Failure for fed cattle in the Texas Panhandle.

Abstract Chronic passive congestive (CPC) livers are reported as one of the most common clinical signs of right-sided Bovine Congestive Heart Failure (BCHF). Genes associated with, specifically chronic passive congestive livers as a means to assess BCHF have yet to be identified in literature. This study aimed to conduct a genome-wide association study (GWAS) to identify regions of the bovine genome associated with the susceptibility to chronic passive congestive livers. Fed cattle harvested at one of four beef processing facilities in the Texas Panhandle were identified at evisceration for exhibiting a CPC liver and muscle samples were collected for genome analysis. Control samples were collected from cattle of similar origin (feedlot and lot/pen) for genome comparison. A GWAS was conducted on 391 crossbred cattle (243 cases, 148 controls) using 95,256 variants. Quality control and filtering were performed using PLINK v1.9, applying standard thresholds for minor allele frequency, Hardy-Weinberg equilibrium, genotyping rate, and individual call rate. Linkage disequilibrium-based pruning was also implemented. After quality control and pruning, 76,556 variants and 387 cattle (240 cases, 147 controls) remained for analysis. Analysis was conducted using GEMMA, employing a linear mixed model with a genetic relationship matrix to account for both population structure and relatedness among individuals. In total, the GWAS identified five loci with suggestive significance (P < 1 × 10^-6) and two significant loci (P < 1 × 10^-8) across different chromosomes. These suggestive loci were located on chromosomes 5, 7, 23, 30, and 4. One of these suggestive loci, located on chromosome 7 (position 68,785,245), is associated with the HAVCR2 gene, which encodes the Hepatitis A virus cellular receptor 2 (TIM-3), a protein involved in modulating immune responses. The most significant association was identified on chromosome 3 (P = 1.10 × 10-9), corresponding to a locus within the LOC100295687 gene, which encodes glutathione S-transferase Mu 1 (GSTM1). A crucial enzyme involved in cellular detoxification, GSTM1 plays a key role in metabolizing reactive oxygen species and electrophilic compounds. It is highly expressed in the liver, where it contributes to protecting against oxidative stress and inflammation, much like conditions commonly encountered by cattle affected by BCHF. In other species, GSTM1 has been implicated in both cardiovascular and hepatic health. Notably, GSTM1 has been associated with cardiovascular health, as individuals lacking the GSTM1 gene have been shown to have an increased risk of cardiovascular diseases. Another significant locus on chromosome 4 had a p-value of 7.33 × 10^-8 and is not located within any annotated gene, which may indicate involvement in regulatory or non-coding functions. This genome-wide association study identified promising genetic leads for understanding susceptibility to chronic passive congestive liver in cattle with congestive heart failure.