Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse

Introduction: Spontaneous rupture of tendons and ligaments is common in several species including humans. In horses, degenerative suspensory ligament desmitis (DSLD) is an important acquired idiopathic disease of a major energy-storing tendon-like structure. DSLD risk is increased in several breeds, including the Peruvian Horse. Affected horses have often been used for breeding before the disease is apparent. Breed predisposition suggests a substantial genetic contribution, but heritability and genetic architecture of DSLD have not been determined.
Methods: To identify genomic regions associated with DSLD, we recruited a reference population of 183 Peruvian Horses, phenotyped as DSLD cases or controls, and undertook a genome-wide association study (GWAS), a regional window variance analysis using local genomic partitioning, a signatures of selection (SOS) analysis, and polygenic risk score (PRS) prediction of DSLD risk. We also estimated trait heritability from pedigrees.
Results: Herit..., Peruvian Horses were recruited with IACUC approval and phenotyped as degenerative suspensory ligament desmitis cases or phenotype-negative controls. Genome-wide SNP genotypes were generated from DNA samples that were assayed using an equine genotyping array., Plink binary file sets can be analyzed with PLINK or other similar analytical software.

引言：肌腱与韧带自发性断裂在包括人类在内的多个物种中均较为常见。在马属动物中，退行性悬韧带炎（degenerative suspensory ligament desmitis, DSLD）是一类发生于主要储能类肌腱样结构的重要获得性特发性疾病。包括秘鲁马在内的多个品种均存在DSLD发病风险升高的情况。患病马匹往往在病症显现前已被用于繁育。品种易感性提示该疾病存在显著遗传贡献，但目前尚未明确DSLD的遗传力与遗传结构。
方法：为鉴定与DSLD相关的基因组区域，本研究招募了183匹秘鲁马作为参考群体，通过表型分型将其划分为DSLD病例组与对照组，并开展了全基因组关联分析（genome-wide association study, GWAS）、基于局部基因组分区的区域窗口方差分析、选择信号（signatures of selection, SOS）分析以及DSLD发病风险的多基因风险评分（polygenic risk score, PRS）预测。此外，本研究还通过系谱估算了该性状的遗传力。
结果：[原文此处存在截断]，本研究在获得动物实验伦理审查委员会（Institutional Animal Care and Use Committee, IACUC）批准后招募秘鲁马，将其表型分型为退行性悬韧带炎病例组与表型阴性对照组。通过马属动物基因分型芯片检测DNA样本，获得全基因组单核苷酸多态性（single nucleotide polymorphism, SNP）基因型数据。PLINK二进制文件集可通过PLINK或其他同类分析软件进行分析。