McGivney Charlotte L, McGivney Beatrice A, Farries Gabriella, Gough Katie F, Han Haige, Holtby Amy R, MacHugh David E, Katz Lisa Michelle, Hill Emmeline W
UCD School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
Plusvital Ltd., The Highline, Dun Laoghaire Industrial Estate, Dublin, Ireland.
Equine Vet J. 2025 Jul;57(4):943-952. doi: 10.1111/evj.14461. Epub 2025 Jan 10.
Equine recurrent laryngeal neuropathy (RLN) is an economically important upper respiratory tract (URT) disease with a genetic contribution to risk, but genetic variants independent of height have not been identified for Thoroughbreds. The method of clinical assessment for RLN is critical to accurately phenotype groups for genetic studies.
To identify genetic risk loci for RLN in Thoroughbreds in a genome-wide association study (GWAS) following high-resolution phenotyping.
Case-control.
Thoroughbred horses were characterised as RLN cases and controls using resting and exercising URT endoscopic examinations and laryngeal ultrasonography, with the case-cohort supplemented using a questionnaire. Genotypes for 43 831 autosomal single-nucleotide polymorphisms (SNPs) from n = 235 horses (n = 110 cases; n = 125 controls) were used to estimate trait heritability and identify significantly associated SNPs in a GWAS. Haplotypes were examined in cases and controls and risk allele frequencies were examined in a population cohort (n = 3126).
Heritability was h = 0.30 including sex and 5PCs as covariates. A SNP on ECA20 located between candidate genes, DAAM2 and LRFN2, was significantly associated with RLN. Six index SNPs with allelic effect sizes OR = 1.5-2.9 were identified on ECA1, ECA14, and ECA20 close to candidate genes ATPA10, KCNN2, and TFAP2A. Eleven ECA20 SNPs defined seven haplotypes with homozygous H2/H2 horses having a 3.1× higher risk of RLN. Risk alleles segregate in the population, and stallions are carriers.
The main study population was young. Horses in the control group had no evidence of RLN as 2- or 3-year olds but may have developed RLN later.
Genetic markers for RLN were identified which may be useful for the development of a polygenic risk score. Candidate genes with functions in neuropathies may further the understanding of RLN pathobiology.
马复发性喉神经麻痹（RLN）是一种具有重要经济意义的上呼吸道（URT）疾病，其发病风险具有遗传因素，但尚未确定纯种马中独立于身高的遗传变异。RLN的临床评估方法对于准确划分遗传研究的表型组至关重要。
在进行高分辨率表型分析后，通过全基因组关联研究（GWAS）确定纯种马中RLN的遗传风险位点。
病例对照研究。
使用静息和运动时的URT内镜检查及喉部超声检查，将纯种马分为RLN病例组和对照组，并用问卷对病例队列进行补充。对n = 235匹马（n = 110例病例；n = 125例对照）的43831个常染色体单核苷酸多态性（SNP）进行基因分型，以估计性状遗传力并在GWAS中鉴定显著相关的SNP。在病例组和对照组中检查单倍型，并在一个群体队列（n = 3126）中检查风险等位基因频率。
以性别和5个主成分作为协变量时，遗传力h = 0.30。位于候选基因DAAM2和LRFN2之间的ECA20上的一个SNP与RLN显著相关。在ECA1、ECA14和ECA20上靠近候选基因ATPA10、KCNN2和TFAP2A处，鉴定出6个等位基因效应大小OR = 1.5 - 2.9的索引SNP。11个ECA20 SNP定义了7种单倍型，纯合H2/H2马患RLN的风险高3.1倍。风险等位基因在群体中分离，种公马是携带者。
主要研究群体年轻。对照组中的马在2岁或3岁时没有RLN的证据，但之后可能会发生RLN。
确定了RLN的遗传标记，这可能有助于多基因风险评分的开发。在神经病变中具有功能的候选基因可能会进一步加深对RLN病理生物学的理解。
