TY - JOUR

T1 - A genetic investigation of equine recurrent uveitis in the Icelandic horse breed

AU - Hack, Yael

AU - Henriksen, Michala de Linde

AU - Pihl, Tina Holberg

AU - Nielsen, Rikke Krarup

AU - Dwyer, Ann E.

AU - Bellone, Rebecca R.

N1 - Publisher Copyright: © 2022 Stichting International Foundation for Animal Genetics.

PY - 2022

Y1 - 2022

N2 - Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty-six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case–control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2_141650; NC_009154.3:g.3817009A>G) that reached genome-wide significance (p = 1.79 × 10−7). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC_009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses.

AB - Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty-six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case–control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2_141650; NC_009154.3:g.3817009A>G) that reached genome-wide significance (p = 1.79 × 10−7). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC_009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses.

KW - genome-wide association study

KW - horses

KW - ocular disease

KW - ophthalmology

KW - TIMP2

U2 - 10.1111/age.13200

DO - 10.1111/age.13200

M3 - Comment/debate

C2 - 35451153

AN - SCOPUS:85128503680

VL - 53

SP - 436

EP - 440

JO - Animal Genetics

JF - Animal Genetics

SN - 0268-9146

IS - 3

ER -