title: Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.
abstract: Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were 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. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.
authors.forename: S L
authors.initials: SL
authors.lastname: Lewis
authors.forename: H M
authors.initials: HM
authors.lastname: Holl
authors.forename: C
authors.initials: C
authors.lastname: Streeter
authors.forename: C
authors.initials: C
authors.lastname: Posbergh
authors.forename: B J
authors.initials: BJ
authors.lastname: Schanbacher
authors.forename: N J
authors.initials: NJ
authors.lastname: Place
authors.forename: M F
authors.initials: MF
authors.lastname: Mallicote
authors.forename: M T
authors.initials: MT
authors.lastname: Long
authors.forename: S A
authors.initials: SA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D009765:Obesity / Q000235:genetics / Q000662:veterinary*