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

Lingaas, Frode; Tengvall, Katarina; Jansen, J. H.; Pelander, Lena; Hurst, M.; Meuwissen, Theo H. E.; Karlsson, Åsa; Meadows, Jennifer R. S.; Sundström, Elisabeth; Thoresen, S. I.; Arnet, E. F.; Guttersrud, Ole Albert; Kierczak, Marcin; Hytönen, Marjo K.; Lohi, Hannes; Hedhammar, Åke; Lindblad‐Toh, Kerstin; Wang, Chao

doi:10.1371/journal.pgen.1010599

Cited by 5 publications

(3 citation statements)

References 81 publications

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“…Almost half of all constrained bases had no functional annotations in any ENCODE cell types ( Christmas et al 2023 ), highlighting the difficulty of identifying functional DNA elements through epigenomic profiling alone. Importantly, human GWAS SNP heritability and canine disease mutations were both enriched within constrained sites ( Meadows et al 2023 ; Sullivan et al 2023 ), indicating that genomic constraint will aid in prioritizing noncoding variation for trait mapping within the dog's characteristic large LD blocks ( Tengvall et al 2022 ; Lingaas et al 2023 ).…”

Section: Interpretation Of Variant Effectsmentioning

confidence: 99%

Large-scale genomic analysis of the domestic dog informs biological discovery

Buckley,

Ostrander

2024

Genome Res.

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Recent advances in genomics, coupled with a unique population structure and remarkable levels of variation, have propelled the domestic dog to new levels as a system for understanding fundamental principles in mammalian biology. Central to this advance are more than 350 recognized breeds, each a closed population that has undergone selection for unique features. Genetic variation in the domestic dog is particularly well characterized compared with other domestic mammals, with almost 3000 high-coverage genomes publicly available. Importantly, as the number of sequenced genomes increases, new avenues for analysis are becoming available. Herein, we discuss recent discoveries in canine genomics regarding behavior, morphology, and disease susceptibility. We explore the limitations of current data sets for variant interpretation, tradeoffs between sequencing strategies, and the burgeoning role of long-read genomes for capturing structural variants. In addition, we consider how large-scale collections of whole-genome sequence data drive rare variant discovery and assess the geographic distribution of canine diversity, which identifies Asia as a major source of missing variation. Finally, we review recent comparative genomic analyses that will facilitate annotation of the noncoding genome in dogs.

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Section: Interpretation Of Variant Effectsmentioning

confidence: 99%

Large-scale genomic analysis of the domestic dog informs biological discovery

Buckley,

Ostrander

2024

Genome Res.

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“…The disease affected every canine age group, with a higher prevalence in older individuals (Kokkinos et al., 2022 ; O'Neill et al., 2013 ). Various causes were identified for this progressive disease, including different infections (e.g., leptospirosis (Di Azevedo et al., 2022 ), babesiosis (Karasová et al., 2022 ), leishmaniosis (Giapitzoglou et al., 2020 )), glomerular diseases (Hokamp et al., 2016 ), ischaemic events (Brown et al., 2019 ; Polyak & Grosche, 2008 ), nephrotoxicity (De Santis et al., 2022 ), neoplasia (Crivellenti et al., 2016 ), urinary obstruction (Polzin & Cowgill, 2016 ) and genetic factors (Lingaas et al., 2023 ). Determining the correct etiology of CKD can be challenging ( O'Neill et al., 2013 ; Perini‐Perera et al., 2021 ; Rudinsky et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive analysis of albuminuria in canine chronic kidney disease

Paukner,

Filipejova,

Mareš

et al. 2024

Veterinary Medicine & Sci

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BackgroundAlbuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood.ObjectivesThis study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening.MethodsThe study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined.ResultsThe Pearson's correlation coefficient between log‐transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (μg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension.ConclusionsUAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

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“…Until now, genomic predictions have received little attention in dog breeding. There have been a few studies using genomic SNP data to predict disorders such as canine hip dysplasia [ 22 , 23 ], cranial cruciate ligament rupture [ 24 ], and kidney disease [ 25 ]. Thorsrud et all.…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis and prediction of genomic values for distichiasis in Staffordshire bull terriers

Joergensen¹,

Ropstad²,

Meuwissen³

et al. 2023

Canine Med Genet

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Background Distichiasis is a condition characterized by aberrant hairs along the eyelid margins. The symptoms are usually mild but can lead to ulcerations and lesions of the cornea in severe cases. It is the most frequently noted ocular disorder in Norwegian Staffordshire bull terriers (SBT), with a prevalence above 18% in the adult population. A complex inheritance is assumed, but there is sparse knowledge about the genetic background of distichiasis in dogs. We have performed a genome-wide association study of distichiasis in SBT and used genomic data in an attempt to predict genomic values for the disorder. Results We identified four genetic regions on CFA1, CFA18, CFA32 and CFA34 using a mixed linear model association analysis and a Bayesian mixed model analysis. Genomic values were predicted using GBLUP and a Bayesian approach, BayesR. The genomic prediction showed that the 1/4 of dogs with predicted values most likely to acquire distichiasis had a 3.9 -4.0 times higher risk of developing distichiasis compared to the quarter (1/4) of dogs least likely to acquire the disease. There was no significant difference between the two methods used. Conclusion Four genomic regions associated with distichiasis were discovered in the association analysis, suggesting that distichiasis in SBT is a complex trait involving numerous loci. The four associated regions need to be confirmed in an independent sample. We also used all 95 K SNPs for genomic prediction and showed that genomic prediction can be a helpful tool in selective breeding schemes at breed level aiming at reducing the prevalence of distichiasis in SBTs in the future, even if the predictive value of single dogs may be low.

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

Cited by 5 publications

References 81 publications

Large-scale genomic analysis of the domestic dog informs biological discovery

Large-scale genomic analysis of the domestic dog informs biological discovery

A comprehensive analysis of albuminuria in canine chronic kidney disease

Genomic analysis and prediction of genomic values for distichiasis in Staffordshire bull terriers

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