Table 1. Genome sequence context for JMJD1C SNPs associated with bovine congestive heart failure (BCHF)

<strong>Background:</strong>  The power and resolution of genome-wide association studies (GWAS) may be enhanced with increased DNA marker density and reduced ascertainment bias of whole genome sequence (WGS) technology compared to that of bead-based microarrays.  However, validation of WGS marker associations may be challenging since preexisting assays for these variants will not always be available.  Here, our aim was to provide preliminary molecular, genetic, and statistical information for JMJD1C variants associated with bovine congestive heart failure (BCHF) for the purpose of assay development.
<strong>Methods: </strong> A WGS data set with greater than 10-fold genome coverage per animal was generated from 102 BCHF matched case-control pairs.  Paired nominal data from 11 million single nucleotide polymorphisms (SNPs), filtered for frequency and quality, were analyzed with McNemar’s test and sorted genome-wide by false discovery rate (FDR).
<strong>Results:</strong>   A 45 kb region spanning introns 2 and 3 of JMJD1C on chromosome 28 was identified as being significantly associated with BCHF with a FDR q-value less than 0.05.  This association was in addition to those in ARRDC3 and NFIA previously reported (Heaton et al. F1000Research 2022, 11:385).  Nine linked SNPs in JMJD1C comprised exactly two haplotypes with an average minor allele frequency (MAF) of 0.005 and 0.132 in the cases and controls, respectively.  Two copies of the major SNP alleles were associated with disease development, while one or two copies of the minor SNP alleles were not.   There were 25 informative pairs for each of the nine linked SNPs, and the “protective” allele was absent from all 25 diseased animals in these informative pairs (McNemar’s b/c = 0/25, OR = 0, mid p-value = 3.0 x 10E-8, FDR = 9.8 x 10E-3).
 <strong>Conclusion:</strong> These preliminary results indicate that selection for the protective JMJD1C  alleles may be useful in reducing BCHF in severely affected herds, however genotype assay development will be needed for further validation.   The marker details are publicly available for use without restriction (https://doi.org/10.6084/m9.figshare.19780558.v1).