Genome-wide association study of osteochondrosis in the tarsocrural joint of Dutch Warmblood horses identifies susceptibility loci on chromosomes 3 and 10 N. Orr 1,2,† , E. W. Hill 1 , J. Gu 1 , P. Govindarajan 1 , J. Conroy 3 , E. M. van Grevenhof 4 , B. J. Ducro 4 , J. A. M van Arendonk 4 , J. H. Knaap 5 , P. R. van Weeren 6 , D. E. MacHugh 1 , S. Ennis 3 and P. A. J. Brama 2 1 Animal Genomics Laboratory, School of Agriculture and Food Science, University College Dublin, Dublin, Ireland. 2 Section of Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Dublin, Ireland. 3 School of Medicine & Medical Science, University College Dublin, Dublin, Ireland. 4 Animal Breeding and Genomics Centre, Wageningen University and Research Centre, Wageningen, The Netherlands. 5 Royal Dutch Sporthorse (KWPN), Harderwijk, The Netherlands. 6 Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Summary Equine osteochondrosis is a developmental joint disease that is a significant source of morbidity affecting multiple breeds of horse. The genetic variants underlying osteochon- drosis susceptibility have not been established. Here, we describe the results of a genome- wide association study of osteochondrosis using 90 cases and 111 controls from a population of Dutch Warmblood horses. We report putative associations between osteochondrosis and loci on chromosome 3 (BIEC2-808543; P = 5.03 9 10 7 ) and chromosome 10 (BIEC2-121323; P = 2.62 9 10 7 ). Keywords Equus caballus, Orthopaedic disease, SNP Introduction Osteochondrosis (OC) is an osteoarticular disorder that arises due to aberrations in endochondral ossification and is a frequent cause of aseptic joint inflammation and lameness in young horses (Rejno & Stromberg 1978). Osteochondral lesions may predispose for the development of osteoarthritis at a later age (Brama 2009; van Weeren 2012). OC is characterised by irregularities in the ossification process that lead to locally thickened cartilage plugs (Brama 2009; van Weeren 2012). Clinically, the condition is characterised by joint distension and sometimes by lameness in young athletic individuals (Brama 2009; van Weeren 2012). Osteochondrosis is most commonly diagnosed in tarsoc- rural (TC), femoropatellar (FP) and metacarpophalangeal (MCP) joints, but has been described in almost every diarthrodial joint (van Weeren & Barneveld 1999). In Warmblood horses, most research has focused on the TC (hock) joint, where the incidence of OC is highest and where there is little controversy about the phenotypic appearance of OC. In this joint, commonly affected predilection sites include the cranial apex of the distal intermediate ridge of the tibia, the distal end of the lateral trochlear ridge of the talus and the medial malleolus of the distal tibia (McIlwraith et al. 2005; Brama 2009; van Grevenhof et al. 2009a; van Weeren 2012). Heritability estimates for OC vary both by breed and by joint, suggesting that they may not necessarily share the same genetic risk factors (Wittwer et al. 2007; van Grevenhof et al. 2009b). Furthermore, environmental fac- tors are implicated in the aetiology of OC (Barneveld & van Weeren 1999; Sloet van et al. 1999; van Weeren & Barneveld 1999; van Weeren et al. 1999). Microsatellite- based whole-genome scans have identified putative quan- titative trait loci on a number of different chromosomes that showed suggestive association with OC (Dierks et al. 2007; Wittwer et al. 2008, 2009). Three recent genome- wide association studies (GWASs) conducted using the Illumina EquineSNP50 genotyping array have reported associations between SNPs and OC in Norwegian Stan- dardbred Trotters, French Trotters and Thoroughbreds (Lykkjen et al. 2010; Corbin et al. 2012; Teyssedre et al. 2012), but there is no clear evidence of replication of the loci identified. In the current study, we conducted a GWAS Address for correspondence P. Brama, Section of Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Dublin, Ireland. E-mail: Pieter.Brama@ucd.ie Current Address: † The Breakthrough Breast Cancer Research Centre The Institute of Cancer Research Fulham Road London SW3 6JB UK Accepted for publication 21 October 2012 doi: 10.1111/age.12016 408 © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics, 44, 408–412