Genome Wide Association Study Reveals a Risk Locus for Equine Metabolic Syndrome in the Arabian Horse

Obesity is the leading risk factor for equine metabolic syndrome (EMS), a condition primarily characterized by hyperinsulinemia and severe laminitis. Early identification of at-risk individuals is crucial for implementation of preventative measures as effective treatments for EMS are limited. A genome-wide association study (GWAS) using Arabian horses with severe laminitis secondary to EMS (with or without concurrent PPID) revealed significant genetic markers near a single candidate gene (FAM174A) hypothesized to play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T>C) correlated with elevated insulin values and increased frequency of laminitis (p=0.0024, p=0.0001). In a second population, the BIEC2-263524 marker maintained its associations with elevated insulin values (p=0.0083) and higher body condition scores (BCS) (p=0.0045). Screening of the predicted FAM174A coding regions by sequencing identified a polymorphic homopolymer in the 3’ untranslated region (UTR) that correlated with elevated insulin values in the GWAS population (p=0.0008) and with elevated insulin, increased BCS, and triglycerides in the second population (p=0.0082, p=0.0116 and p=0.200). The BIEC-263524 –C and the FAM174A 3’UTR -11(G) polymorphisms correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150 kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity and secondary laminitis. Additionally, additional work describing the function of FAM174A may improve our understanding of the etiology of this troubling illness in the horse, and warrants investigation of this locus for a role in homologous metabolic disorders of other species.