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Abstract
The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1–47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8–78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine.
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1 Unit of Animal Genomics, GIGA Institute, University of Liège, Liège, Belgium (GRID:grid.4861.b) (ISNI:0000 0001 0805 7253); RIKEN Center for Integrative Medical Sciences, Laboratory for Genotyping Development, Kanagawa, Japan (GRID:grid.4861.b)
2 Unit of Animal Genomics, GIGA Institute, University of Liège, Liège, Belgium (GRID:grid.4861.b) (ISNI:0000 0001 0805 7253); University of Liège, Department of Clinical Sciences, Faculty of Veterinary Medicine, Liège, Belgium (GRID:grid.4861.b) (ISNI:0000 0001 0805 7253)
3 University of Helsinki, Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)
4 Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X)
5 The Danish Kennel Club, Solrød Strand, Denmark (GRID:grid.5254.6)
6 U955 - IMRB Inserm and Unité de Cardiologie d’Alfort (UCA), Université Paris-Est, École Nationale Vétérinaire d’Alfort, UPEC, 7 avenue du général de Gaulle, Maisons-Alfort, F-94700, France (GRID:grid.410511.0) (ISNI:0000 0001 2149 7878)
7 U955 - IMRB, Biology of the neuromuscular system, Inserm, National Veterinary School of Alfort (ENVA), Maisons-Alfort, France (GRID:grid.457369.a)
8 University of Helsinki, Folkhälsan Research Center, Department of Veterinary Biosciences, Department of Medical and Clinical Genetics, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)