Genome wide association study of 40 clinical measurements in eight dog breeds

Yukihide Momozawa,Merete Fredholm,Helle Friis Proschowsky,Laurent Tiret,Michel Georges,Géraldine Battaille,Valérie Chetboul,Hannes Lohi,Anne-Christine Merveille,Eija H Seppälä,Jørgen Koch,Vassiliki Gouni,Anne-Sophie Lequarré,Jakob Lundgren Willesen,Maria Wiberg

doi:10.1038/s41598-020-63457-y

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.

Highlights

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans
A total of 472 dogs were genotyped using a 170 K Illumina HD canine single nucleotide polymorphism (SNP) array[19] and 145,741 SNPs were selected after quality control (QC)
Taking advantage of the possibility to analyze each dog breed in our study, we investigated a lead SNP in each breed

Summary

Introduction

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. 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. 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. The diagnosis of a disease often involves taking many clinical measurements including blood and urine analysis These measurements directly reflect different aspects of the health of each individual. We conducted breed specific GWAS and its meta-analysis with the 40 measurements in order to reveal the genetic contribution underlying individual differences

Methods

Results

Conclusion