Identification by whole genome sequencing of genes associated with delayed postoperative hemorrhage in Scottish deerhounds

Abstract

Background: Delayed postoperative hemorrhage (DEPOH) is an important health concern for Scottish deerhounds. Hypothesis/Objectives: Identify genes associated with DEPOH in Scottish deerhounds. Animals: Two hundred sixty-nine privately owned Scottish deerhounds. Methods: Retrospective case-control study. DEPOH cases and controls were identified through an owner health survey. Genome-wide association analysis was performed using whole genome sequences from 8 cases and 17 controls. All cases and controls were genotyped for selected variants. Results: Of 269 dogs, 10 met inclusion and exclusion criteria for DEPOH, while 62 controls had undergone similar surgical procedures without DEPOH. Genome-wide association analysis identified a single locus on chromosome 9 spanning 40 genes. One of these genes (SERPINF2 encoding alpha-2 antiplasmin) was directly linked to the pathophysiology of DEPOH. The entire cohort was genotyped for a missense SERPINF2 variant (c.605 C>T; p.A202V). Compared to dogs with the reference C/C genotype, the likelihood of DEPOH was significantly higher for dogs with the T/T genotype (odds ratio [OR] = 1235; 95% confidence interval [CI] = 23-6752; P = 0.0005) and with the C/T genotype (OR = 28; 95% CI = 1.4-542; P = 0.03). Conclusions and Clinical Importance: SERPINF2 is associated with DEPOH in Scottish deerhounds. Genetic testing might be able to identify dogs that are susceptible to DEPOH.