Bayesian mixed model analysis uncovered 21 risk loci for chronic kidney disease in boxer dogs
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
DOI:
10.1371/journal.pgen.1010599
Publication Date:
2023-01-24T18:34:11Z
AUTHORS (18)
ABSTRACT
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 in nearly all breeds, but its genetic basis remains unclear. Here, we performed a Bayesian mixed model genome-wide association analysis for canine CKD in a boxer population of 117 canine cases and 137 controls, and identified 21 genetic regions associated with the disease. At the top markers from each CKD region, the cases carried an average of 20.2 risk alleles, significantly higher than controls (15.6 risk alleles). An ANOVA test showed that the 21 CKD regions together explained 57% of CKD phenotypic variation in the population. Based on whole genome sequencing data of 20 boxers, we identified 5,206 variants in LD with the top 50 BayesR markers. Following comparative analysis with human regulatory data, 17 putative regulatory variants were identified and tested with electrophoretic mobility shift assays. In total four variants, three intronic variants from theMAGI2andGALNT18genes, and one variant in an intergenic region on chr28, showed alternative binding ability for the risk and protective alleles in kidney cell lines. Many genes from the 21 CKD regions,RELN,MAGI2,FGFR2and others, have been implicated in human kidney development or disease. The results from this study provide new information that may enlighten the etiology of CKD in both dogs and humans.
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