Marginal ancestral contributions to atrial fibrillation in the Standardbred racehorse: Comparison of cases and controls

Abstract

Admissions of Standardbred racehorses (Std) to the Ontario Veterinary College Teaching Hospital (OVCTH) for treatment of atrial fibrillation (AF) began to increase in the early 1990s. The arrhythmia has been shown to have a modest heritability (h2 ≃ 0.15), with some stallions appearing as sires or sires of mares used in breeding (broodmares) of affected horses more frequently than others. The objective of this study was to determine the marginal genetic contributions of ancestors to cohorts of Std affected with AF and their contemporary control groups, and whether these ancestors contribute significantly more to the affected cohorts than to controls. All Std admitted to OVCTH for treatment of AF that were born between 1993 and 2007 comprised the affected case group (n = 168). Five randomly selected racing contemporaries for each Std admitted, assumed to not suffer from the arrhythmia, comprised the control group (n = 840). Three-year overlapping cohorts were created for case and control horses, determined according to year of birth, for a total of 26 cohorts. Marginal genetic contributions of ancestors to each cohort were determined and differences analyzed for statistical significance using a two-tailed paired t-test, with P ≤ 0.05 considered significant. The marginal contributions of 26 ancestors were significant, with 11 contributing significantly more to affected cohorts than the corresponding controls, and 15 contributing significantly more to controls than the corresponding affected cohorts. One stallion and one broodmare were very highly significant to affected cohorts at P ≤ 0.001, and nine stallions and three broodmares were very highly significant to control cohorts at P ≤ 0.001. Therefore, a number of stallions have statistically significant contributions to the genetics of Std affected with AF, while many others have statistically significant contributions to healthy Std. The arrhythmia appears to be particularly prevalent in the descendants of one sire family.

Incidence, recurrence, and outcome of postrace atrial fibrillation in Thoroughbred horses

“…This observation is consistent with studies in horses, in which increased body mass is associated with risk of AF 51,52 . Research in Standardbred racehorses has supported a genetic basis for AF based on epidemiology and pedigree analysis 51,53,54 . Additional studies are needed to determine the role of genetics in AF in Thoroughbreds.…”

Paroxysmal Atrial Fibrillation in Horses: Pathophysiology, Diagnostics and Clinical Aspects

“…A retrospective study from Canada reported that Standardbreds were more commonly affected by AF than other breeds [64]. It was later discovered that AF is a moderately heritable arrhythmia in Standardbreds, and frequently used breeding stallions might have helped increase the incidence, though the mode of inheritance is still unknown [65,66]. A recent study investigating heritability in Thoroughbreds from Hong Kong and Australia found the heritability of AF to be low [67].…”

Fundamentals of arrhythmogenic mechanisms and treatment strategies for equine atrial fibrillation

“…It is a partially heritable disease in humans and a family history of AF increases the risk of developing AF 123 . Heritability of AF has been demonstrated in Standardbred horses 124,125 where some American Standardbred lineages were more often associated with AF. Several genetic variants are linked to human AF including developmental genes like PITX2 and genes involved in metabolic stress responses 123,126,127 .…”