Unveiling Genetic Signatures Associated with Resilience to Neonatal Diarrhea in Lambs Through Dual GWAS Approaches

Abstract Neonatal diarrhea poses a particularly daunting challenge due to its multifactorial etiology, resulting in high morbidity and mortality rates and substantial economic consequences worldwide. Moreover, the zoonotic potential of neonatal diarrhea underscores its importance in public health concerns. Although no molecular-level study has evaluated genetic resistance/susceptibility to neonatal diarrhea in farm animals, previous observations suggest potential avenues for further research. The present study employs two genome-wide association approaches, namely the nonparametric multi-locus (pKWmEB) and the single-locus Mixed Linear Model (MLM), to explore potential associations between genetic variations in innate immunity and neonatal diarrhea in Karacabey Merino lambs. A total of 707 lambs, comprising 180 cases and 527 controls, were analyzed, revealing an overall prevalence rate of 25.5%. Using a multi-locus (pKWmEB) GWA analysis, 13 SNPs surpassing the threshold of ≥ LOD 3 were identified. Additionally, the single-locus MLM approach identified one SNP with an exact p-value of 1.85e-7, and this SNP (s61781.1) in the SLC22A8 gene was co-detected by both methods. Our results demonstrate that besides environmental conditions and management practices, the manifestation of neonatal diarrhea can be explained to some degree by genetic backgrounds, and marker-assisted selection can be a useful complementary tool in the struggle against neonatal diarrhea.