POSTER ABSTRACTS
#47 A genome-wide association study investigating hyperthyroidism in domestic cats P. A. Norman1 , R. E. Jepson1, L. J. Davison1,2, M. D. Wallace1,2 and H. M. Syme1 pnorman3@rvc.ac.uk 1Department of Clinical Services and Sciences, Royal Veterinary College, London, UK, 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK Feline hyperthyroidism (FHT) is the most common feline endocrine disease, affecting up to 10% of geriatric cats. FHT pathogenesis is multi-factorial with environmental, dietary and genetic risk factors. Genome-wide association studies (GWAS) have been widely used in human medicine to determine genetic variants associated with complex disease phenotypes, and more recently the technique has been used to investigate feline hypertension and renal traits. We performed a case-control GWAS utilising the Illumina Infinium iSelect 63K Cat DNA Array to investigate FHT in a discovery cohort of 884 domestic short and long-haired cats. Phenotyping was based on longitudinal veterinary visit data (median (days)= 310.5, LQ=0, UQ=918.8) using a combi- nation of total T4 (TT4) and TSH measurements and use of anti-thyroid treatment. Using Plink v1.9, quality control (QC) and principal components excluded outliers (Mean ± >3SD of PC1 and PC2) and other breeds (n=6). QC resulted in 47,178 variants and 872 cats, comprising 102 cases and 770 controls for additive association testing. Since determination of thyroid status can be impacted by factors such as age and concurrent illness, we produced 3 separate euthyroid control groupings with varying grades of strictness, based on last age at follow-up, and TT4 and TSH measurements: most inclusive (euthyroid, n=770), moderately inclusive (euthyroid, n=527) and most strictly defined (euthyroid, n=423). Some of the significant variants associated with FHT by additive association testing are located in gene regions involved in endoplasmic reticulum maintenance, thyroid hormone synthesis signalling pathways, and thyroid carcinoma. Further analyses are currently underway.
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