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

Abstract

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.

Keywords

• hyperfibrinolysis
• postoperative bleeding
• Scottish deerhound