Bayesian mixed model analysis uncovered 21 risk loci for chronic kidney disease in boxer dogs

• DOI: 10.1371/journal.pgen.1010599
• Publication Date: 2023-01-24T18:34:11Z
• Authors: Frode Lingaas; Katarina Tengvall; Johan Høgset Jansen; Lena Pelander; Maria H. Hurst; Theo Meuwissen; Åsa Karlsson; Jennifer R. S. Me...; Elisabeth Sundström; Stein Istre Thoresen; Ellen Frøysadal A...; Ole Albert Gutter...; Marcin Kierczak; Marjo K. Hytönen; Hannes Lohi; Åke Hedhammar; Kerstin Lindblad-Toh; Chao Wang
• Keywords: 0301 basic medicine; Expression; QH426-470; Kidney; Polymorphism, Single Nucleotide; 630; Medical Genetics and Genomics; Domestication; Association; 03 medical and health sciences; Dogs; Genetics (medical genetics to be 30107 and agricultural genetics to be 40402); Sequence; Genetics; Humans; Animals; Analyses reveal; Genetik; Renal Insufficiency, Chronic; Alleles; Medicinsk genetik; Genome; Juvenile nephropathy; Genetics and Genomics; Genetik och genomik; Bayes Theorem; Medicinsk genetik och genomik; 3. Good health; Biomedicine; Renal dysplasia; Genetics, developmental biology, physiology; Recessive hereditary nephropathy; Polymorphisms; Medical Genetics; Research Article; Genome-Wide Association Study

Chronic kidney disease (CKD) affects 10% of the human population, with only a small fraction genetically defined. CKD is also common in dogs and has been diagnosed nearly all breeds, but its genetic basis remains unclear. Here, we performed Bayesian mixed model genome-wide association analysis for canine boxer population 117 cases 137 controls, identified 21 regions associated disease. At top markers from each region, carried an average 20.2 risk alleles, significantly higher than controls (15.6 alleles). An ANOVA test showed that together explained 57% phenotypic variation population. Based on whole genome sequencing data 20 boxers, 5,206 variants LD 50 BayesR markers. Following comparative regulatory data, 17 putative were tested electrophoretic mobility shift assays. In total four variants, three intronic MAGI2 GALNT18 genes, one variant intergenic region chr28, alternative binding ability protective alleles cell lines. Many genes regions, RELN, MAGI2, FGFR2 others, have implicated development or The results this study provide new information may enlighten etiology both humans.