Publications by authors named "Per Madsen"

87 Publications

Heritability of distichiasis in Havanese dogs in Norway.

Canine Med Genet 2021 Nov 16;8(1):11. Epub 2021 Nov 16.

Center for Quantitative Genetics and Genomics, Aarhus University, dk-8830, Tjele, Denmark.

Background: Distichiasis is a presumed inherited eyelid disease, characterized by misplaced eyelashes. The effect on eye health and animal welfare varies between individuals; most mild cases show no clinical signs, but some affected animals develop painful corneal disease. In this study, we investigated the prevalence and heritability of distichiasis in the Norwegian population of Havanese dogs.

Results: A total of 1156 Havanese were included in the study. Out of these, 168 were affected with distichiasis, making the prevalence in our sample 14.5% (95% CI 12.5-16.6%). There was no sex predisposition. Most affected individuals were graded "mildly affected". The estimates generally showed high heritabilities, which varied between 0.276 (linear model) and 0.720 (Bayesian threshold model). The linear estimates, after conversion to the underlying scale (h = 0.664-0.674), corresponds well to the results of the Bayesian models.

Conclusions: The estimated heritability of distichiasis in Havanese is high and the prevalence is moderate. The high heritability indicate that a significant selection response could be obtained by simple mass selection. To secure good animal welfare, it's important to control the number of affected individuals and especially the severely affected.
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http://dx.doi.org/10.1186/s40575-021-00110-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594152PMC
November 2021

Genotype by climate zone interactions for fertility, somatic cell score, and production in Iranian Holsteins.

J Dairy Sci 2021 Dec 14;104(12):12994-13007. Epub 2021 Sep 14.

Center for Quantitative Genetic and Genomics, Aarhus University, 8830 Tjele, Denmark. Electronic address:

The objective of this study was to investigate genetic variation and genotype by environment (G × E) interactions for fertility (including age at first calving and calving interval), somatic cell score (SCS), and milk production traits for Iranian Holsteins. Different environments were defined based on the climatic zones (cold, semi-cold, and moderate) and considering the herd location. Data were collected between 2003 and 2018 by the National Animal Breeding Center of Iran (Karaj). Variance and covariance components and genetic correlations were estimated using 2 different models, which were analyzed using Bayesian methods. For both models, performance of traits in each climate were considered as different traits. Fertility traits were analyzed using a trivariate model. Furthermore, SCS and production traits were analyzed using trivariate random regression models (records in different climate zones considered as different traits). For the fertility traits, the largest estimates of heritability were observed in cold climate. Fertility performance was always better in cold environment. Genetic correlations between climatic zones ranged from 0.85 to 0.94. For daily measurements of SCS and production traits, heritability ranged from 0.031 to 0.037 and 0.069 to 0.209, respectively. Genetic variances were the highest in the semi-cold and moderate climates for the SCS and production traits, respectively. Furthermore, across the studied climates, 305-d genetic correlation ranged from 0.756 to 0.884 for SCS and from 0.925 to 0.957 for the production traits. The structure of genetic correlation within each climate indicated a negative correlation between early and late lactation for SCS, especially in the cold climate and for milk production in the moderate climate. For fat percentage, in all climatic zones, the lowest genetic correlations were observed between early and mid-lactation. In addition, for protein production in the cold climate, a negative correlation was observed between early and late lactation. Results indicated heterogeneous variance components for all the studied traits across various climatic zones. Estimated genetic correlations for SCS revealed that the genetic expression of animals may vary by climatic zone. Results indicated the existence of G × E interaction due to the climatic condition, only for SCS. Therefore, in Iranian Holsteins, the effect of G × E interactions should not be neglected, especially for SCS, as different sires might be optimal for use in different climatic zones.
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http://dx.doi.org/10.3168/jds.2020-20084DOI Listing
December 2021

Left Ventricular Diastolic Function Studied with Magnetic Resonance Imaging: A Systematic Review of Techniques and Relation to Established Measures of Diastolic Function.

Diagnostics (Basel) 2021 Jul 16;11(7). Epub 2021 Jul 16.

Department of Cardiology, Copenhagen University Hospital, 2730 Herlev, Denmark.

In recent years, cardiac magnetic resonance (CMR) has been used to assess LV diastolic function. In this systematic review, studies were identified where CMR parameters had been evaluated in healthy and/or patient groups with proven diastolic dysfunction or known to develop heart failure with preserved ejection fraction. We aimed at describing the parameters most often used, thresholds where possible, and correlation to echocardiographic and invasive measurements. A systematic literature review was performed using the databases of PubMed, Embase, and Cochrane. In total, 3808 articles were screened, and 102 studies were included. Four main CMR techniques were identified: tagging; time/volume curves; mitral inflow quantification with velocity-encoded phase-contrast sequences; and feature tracking. Techniques were described and estimates were presented in tables. From published studies, peak change of torsion shear angle versus volume changes in early diastole (-dφ'/dV') (from tagging analysis), early peak filling rate indexed to LV end-diastolic volume <2.1 s (from LV time-volume curve analysis), enlarged LA maximal volume >52 mL/m, lowered LA total (<40%), and lowered LA passive emptying fractions (<16%) seem to be reliable measures of LV diastolic dysfunction. Feature tracking, especially of the atrium, shows promise but is still a novel technique. CMR techniques of LV untwisting and early filling and LA measures of poor emptying are promising for the diagnosis of LV filling impairment, but further research in long-term follow-up studies is needed to assess the ability for the parameters to predict patient related outcomes.
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http://dx.doi.org/10.3390/diagnostics11071282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305340PMC
July 2021

Conductance artery stiffness impairs atrio-ventriculo-arterial coupling before manifestation of arterial hypertension or left ventricular hypertrophic remodelling.

Sci Rep 2021 07 14;11(1):14467. Epub 2021 Jul 14.

Department of Cardiology, Herlev-Gentofte Hospital, Herlev, Denmark.

As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV.
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http://dx.doi.org/10.1038/s41598-021-93614-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280135PMC
July 2021

Metabolic improvement with short-term, glucagon-like peptide-1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

Diabetes Obes Metab 2021 10 26;23(10):2374-2384. Epub 2021 Jul 26.

Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Copenhagen, Denmark.

Aim: To investigate if short-term treatment with liraglutide, a glucagon-like peptide-1 receptor agonist, improves left ventricular diastolic function.

Materials And Methods: An investigator-initiated, double-blind, randomized, placebo-controlled trial on the effect of 18 weeks of treatment with liraglutide on diastolic function was assessed in patients with type 2 diabetes with signs of diastolic dysfunction (echo-Doppler determined E/e' ≥ 9 and/or lateral e' ≤ 10 cm/s). Primary outcomes were improved left ventricle filling (the early peak filling rate [ePFR]) and left atrium ease of emptying (the passive emptying fraction [LA ]), assessed by cardiac magnetic resonance imaging at rest and during chronotropic stress. Secondary outcomes included left ventricular and left atrial volumes and systolic function, measures of aortic stiffness and echocardiographic diastolic variables.

Results: Forty patients were randomized to liraglutide subcutaneously 1.8 mg/day (n = 20) or placebo (n = 20). Liraglutide reduced HbA1c (-0.47%, 95% CI [-0.88% to -0.06%] [-5.1, 95% CI {-9.7 to -0.62} mmol/mol]) and weight (-2.9, 95% CI [-4.6 to -1.2] kg); both P < .03. Liraglutide did not change ePFR at rest (-24 ± 60 vs. -6 ± 46 mL/s), during stress (2 ± 58 vs. -2 ± 38 mL/s), or the changes from rest to stress (12.9 ± 72.5 vs. 4.7 ± 104.0; all P > .05). LA decreased with liraglutide during stress (-3.1% [-9.0%, 1.1%] vs. 1.0% [-2.9%, 6.1%]; P = .049), but no changes were evident at rest (-4.3% [-7.9%, 1.9%] vs. -0.6% [-3.1%, 2.2%]; P = .19), or for the changes from rest to stress (-1.7 ± 8.4 vs. 0.8 ± 8.2; P = .4). Secondary outcomes were unchanged by liraglutide.

Conclusions: Short-term treatment with liraglutide did not improve left ventricular diastolic function, suggesting the cardioprotective effect is not exerted through the improvement in diastolic dysfunction.
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http://dx.doi.org/10.1111/dom.14480DOI Listing
October 2021

Genetic parameters and genomic prediction for feed intake recorded at the group and individual level in different production systems for growing pigs.

Genet Sel Evol 2021 Apr 8;53(1):33. Epub 2021 Apr 8.

SEGES, Pig Research Centre, 1609, Copenhagen, Denmark.

Background: In breeding programs, recording large-scale feed intake (FI) data routinely at the individual level is costly and difficult compared with other production traits. An alternative approach could be to record FI at the group level since animals such as pigs are normally housed in groups and fed by a shared feeder. However, to date there have been few investigations about the difference between group- and individual-level FI recorded in different environments. We hypothesized that group- and individual-level FI are genetically correlated but different traits. This study, based on the experiment undertaken in purebred DanBred Landrace (L) boars, was set out to estimate the genetic variances and correlations between group- and individual-level FI using a bivariate random regression model, and to examine to what extent prediction accuracy can be improved by adding information of individual-level FI to group-level FI for animals recorded in groups. For both bivariate and univariate models, single-step genomic best linear unbiased prediction (ssGBLUP) and pedigree-based BLUP (PBLUP) were implemented and compared.

Results: The variance components from group-level records and from individual-level records were similar. Heritabilities estimated from group-level FI were lower than those from individual-level FI over the test period. The estimated genetic correlations between group- and individual-level FI based on each test day were on average equal to 0.32 (SD = 0.07), and the estimated genetic correlation for the whole test period was equal to 0.23. Our results demonstrate that by adding information from individual-level FI records to group-level FI records, prediction accuracy increased by 0.018 and 0.032 compared with using group-level FI records only (bivariate vs. univariate model) for PBLUP and ssGBLUP, respectively.

Conclusions: Based on the current dataset, our findings support the hypothesis that group- and individual-level FI are different traits. Thus, the differences in FI traits under these two feeding systems need to be taken into consideration in pig breeding programs. Overall, adding information from individual records can improve prediction accuracy for animals with group records.
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http://dx.doi.org/10.1186/s12711-021-00624-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028714PMC
April 2021

Accounting for genetic architecture for body weight improves accuracy of predicting breeding values in a commercial line of broilers.

J Anim Breed Genet 2021 Sep 28;138(5):528-540. Epub 2021 Mar 28.

Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, Denmark.

BLUP (best linear unbiased prediction) is the standard for predicting breeding values, where different assumptions can be made on variance-covariance structure, which may influence predictive ability. Herein, we compare accuracy of prediction of four derived-BLUP models: (a) a pedigree relationship matrix (PBLUP), (b) a genomic relationship matrix (GBLUP), (c) a weighted genomic relationship matrix (WGBLUP) and (d) a relationship matrix based on genomic features that consisted of only a subset of SNP selected on a priori information (GFBLUP). We phenotyped a commercial population of broilers for body weight (BW) in five successive weeks and genotyped them using a 50k SNP array. We compared predictive ability of univariate models using conservative cross-validation method, where each full-sib group was divided into two folds. Results from cross-validation showed, with WGBLUP model, a gain in accuracy from 2% to 7% compared with GBLUP model. Splitting the additive genetic matrix into two matrices, based on significance level of SNP (G : estimated with only set of SNP selected on significance level, G : estimated with the remaining SNP), led to a gain in accuracy from 1% to 70%, depending on the proportion of SNP used to define G . Thus, information from GWAS in models improves predictive ability of breeding values for BW in broilers. Increasing the power of detection of SNP effects, by acquiring more data or improving methods for GWAS, will help improve predictive ability.
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http://dx.doi.org/10.1111/jbg.12546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451786PMC
September 2021

On the accuracy and applicability of a new implicit Taylor method and the high-order spectral method on steady nonlinear waves.

Proc Math Phys Eng Sci 2020 Nov 25;476(2243):20200436. Epub 2020 Nov 25.

Department of Mechanical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark.

This paper presents an investigation and discussion of the accuracy and applicability of an implicit Taylor (IT) method versus the classical higher-order spectral (HOS) method when used to simulate two-dimensional regular waves. This comparison is relevant, because the HOS method is in fact an explicit perturbation solution of the IT formulation. First, we consider the Dirichlet-Neumann problem of determining the vertical velocity at the free surface given the surface elevation and the surface potential. For this problem, we conclude that the IT method is significantly more accurate than the HOS method when using the same truncation order, , and spatial resolution, , and is capable of dealing with steeper waves than the HOS method. Second, we focus on the problem of integrating the two methods in time. In this connection, it turns out that the IT method is less robust than the HOS method for similar truncation orders. We conclude that the IT method should be restricted to  = 4, while the HOS method can be used with  ≤ 8. We systematically compare these two options and finally establish the best achievable accuracy of the two methods as a function of the wave steepness and the water depth.
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http://dx.doi.org/10.1098/rspa.2020.0436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735293PMC
November 2020

Impact of the Order of Legendre Polynomials in Random Regression Model on Genetic Evaluation for Milk Yield in Dairy Cattle Population.

Front Genet 2020 5;11:586155. Epub 2020 Nov 5.

Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, Denmark.

The random regression test-day model has become the most commonly adopted model for routine genetic evaluations in dairy populations, which allows accurately accounting for genetic and environmental effects over lactation. The objective of this study was to explore appropriate random regression test-day models for genetic evaluation of milk yield in a Holstein population with a relatively small size, which is the common situation in regional or independent breeding companies to preform genetic evaluation. Data included 419,567 test-day records from 54,417 cows from the first lactation. Variance components and breeding values were estimated using a random regression test-day model with different orders (from first to fifth) of Legendre polynomials (LP) and accounted for homogeneous or heterogeneous residual variance across the lactation. Models were compared based on Akaike information criterion (AIC), Bayesian information criterion (BIC), and predictive ability. In general, models with a higher order of LP showed better goodness of fit based on AIC and BIC values. However, models with third, fourth, and fifth order of LP led to similar estimates of genetic parameters and predictive ability. Models with assumption of heterogeneous residual variances achieved better goodness of fit but yielded similar predictive ability compared with those with assumption of homogeneous residual variances. Therefore, a random regression model with third order of LP is suggested to be an appropriate model for genetic evaluation of milk yield in local Chinese Holstein populations.
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http://dx.doi.org/10.3389/fgene.2020.586155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674963PMC
November 2020

[Nobelprisen i fysiologi eller medicin 2019].

Ugeskr Laeger 2020 10;182(44)

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October 2020

Distinct non-ischemic myocardial late gadolinium enhancement lesions in patients with type 2 diabetes.

Cardiovasc Diabetol 2020 10 22;19(1):184. Epub 2020 Oct 22.

Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Capital Region of Denmark, Herlev-Gentofte, Denmark.

Background: Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM.

Methods: 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T-mapping and LGE.

Results: 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e'(9.9 IQR8.7-12.6 vs. 8.8 IQR7.4-10.7, P = 0.04), left atrial maximal volume (102 IQR84.6-115.2 vs. 91 IQR75.2-100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9-19.7 vs. 5.9 IQR5.9-10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0-26.1 vs. 13.0 IQR13.0-14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005).

Conclusion: A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331.
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http://dx.doi.org/10.1186/s12933-020-01160-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583253PMC
October 2020

Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics.

Cardiovasc Diabetol 2020 09 30;19(1):158. Epub 2020 Sep 30.

Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200, Slagelse, Region Zealand, Denmark.

Background: The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes.

Methods: In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m were excluded.

Results: Median (Q1-Q3) FGF-23 was 74 (58-91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R = 0.11) and increased E/e* (P < 0.01, R = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57-86) vs. 80 (60-98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues.

Conclusions: In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.
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http://dx.doi.org/10.1186/s12933-020-01135-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528463PMC
September 2020

Cardiac magnetic resonance imaging with standard imaging planes for mitral valve scallop pathology: interrater agreement and comparison with echocardiography.

Int J Cardiovasc Imaging 2021 Feb 24;37(2):605-611. Epub 2020 Sep 24.

Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.

Magnetic resonance imaging (CMR) is applied in mitral valve regurgitation (MR) to quantify regurgitation volume/fraction and cardiac volumes, but individual scallop pathology is evaluated by echocardiography. To evaluate CMR for determination of individual scallop pathology, interrater variability on evaluation of scallop pathology from echocardiography and a standard clinical CMR protocol including a transversal stack was compared. 318 mitral scallops from 53 patients with primary MR were evaluated by two cardiologists evaluating echocardiography scans and two other cardiologists evaluating CMR scans (blinded). Inter-rater variability was determined with percentage agreement and Cohen's kappa. In evaluable scallops, interrater agreement on the diagnosis of a prolapsing and/or flail scallop was 77-87% and kappa values of 0.27-0.67, irrespective of physician or modality. Important differences between modalities were primarily related to CMR-evaluators judging the A3 and the P3 to be normal when echocardiography demonstrated prolapsing or even flail scallops; poor imaging of calcification; and flailed scallops occasionally being undetected with CMR since the flow-voids may mask the scallop. Inter-rater agreement for scallop pathology in primary MR is comparable for echocardiography and standard magnetic resonance imaging scans, but CMR has important pitfalls relating to evaluation of A3 and P3 scallops, and suffers from poor visualization of calcification and lower spatial resolution than echo. CMR with standard planes cannot replace CMR with longitudinal planes or echo for the evaluation of specific scallop pathology in severe primary MR.
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http://dx.doi.org/10.1007/s10554-020-02022-0DOI Listing
February 2021

The relative effect of genomic information on efficiency of Bayesian analysis of the mixed linear model with unknown variance.

J Anim Breed Genet 2021 Jan 30;138(1):14-22. Epub 2020 Jul 30.

Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, Denmark.

This work focuses on the effects of variable amount of genomic information in the Bayesian estimation of unknown variance components associated with single-step genomic prediction. We propose a quantitative criterion for the amount of genomic information included in the model and use it to study the relative effect of genomic data on efficiency of sampling from the posterior distribution of parameters of the single-step model when conducting a Bayesian analysis with estimating unknown variances. The rate of change of estimated variances was dependent on the amount of genomic information involved in the analysis, but did not depend on the Gibbs updating schemes applied for sampling realizations of the posterior distribution. Simulation revealed a gradual deterioration of convergence rates for the locations parameters when new genomic data were gradually added into the analysis. In contrast, the convergence of variance components showed continuous improvement under the same conditions. The sampling efficiency increased proportionally to the amount of genomic information. In addition, an optimal amount of genomic information in variance-covariance matrix that guaranty the most (computationally) efficient analysis was found to correspond a proportion of animals genotyped ***0.8. The proposed criterion yield a characterization of expected performance of the Gibbs sampler if the analysis is subject to adjustment of the amount of genomic data and can be used to guide researchers on how large a proportion of animals should be genotyped in order to attain an efficient analysis.
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http://dx.doi.org/10.1111/jbg.12497DOI Listing
January 2021

Prediction of breeding values for group-recorded traits including genomic information and an individually recorded correlated trait.

Heredity (Edinb) 2021 01 14;126(1):206-217. Epub 2020 Jul 14.

Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, 8830, Tjele, Denmark.

Records on groups of individuals could be valuable for predicting breeding values when a trait is difficult or costly to measure on single individuals, such as feed intake and egg production. Adding genomic information has shown improvement in the accuracy of genetic evaluation of quantitative traits with individual records. Here, we investigated the value of genomic information for traits with group records. Besides, we investigated the improvement in accuracy of genetic evaluation for group-recorded traits when including information on a correlated trait with individual records. The study was based on a simulated pig population, including three scenarios of group structure and size. The results showed that both the genomic information and a correlated trait increased the accuracy of estimated breeding values (EBVs) for traits with group records. The accuracies of EBV obtained from group records with a size 24 were much lower than those with a size 12. Random assignment of animals to pens led to lower accuracy due to the weaker relationship between individuals within each group. It suggests that group records are valuable for genetic evaluation of a trait that is difficult to record on individuals, and the accuracy of genetic evaluation can be considerably increased using genomic information. Moreover, the genetic evaluation for a trait with group records can be greatly improved using a bivariate model, including correlated traits that are recorded individually. For efficient use of group records in genetic evaluation, relatively small group size and close relationships between individuals within one group are recommended.
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http://dx.doi.org/10.1038/s41437-020-0339-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852592PMC
January 2021

Effect of genomic selection and genotyping strategy on estimation of variance components in animal models using different relationship matrices.

Genet Sel Evol 2020 Jun 11;52(1):31. Epub 2020 Jun 11.

Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.

Background: The traditional way to estimate variance components (VC) is based on the animal model using a pedigree-based relationship matrix (A) (A-AM). After genomic selection was introduced into breeding programs, it was anticipated that VC estimates from A-AM would be biased because the effect of selection based on genomic information is not captured. The single-step method (H-AM), which uses an H matrix as (co)variance matrix, can be used as an alternative to estimate VC. Here, we compared VC estimates from A-AM and H-AM and investigated the effect of genomic selection, genotyping strategy and genotyping proportion on the estimation of VC from the two methods, by analyzing a dataset from a commercial broiler line and a simulated dataset that mimicked the broiler population.

Results: VC estimates from H-AM were severely overestimated with a high proportion of selective genotyping, and overestimation increased as proportion of genotyping increased in the analysis of both commercial and simulated data. This bias in H-AM estimates arises when selective genotyping is used to construct the H-matrix, regardless of whether selective genotyping is applied or not in the selection process. For simulated populations under genomic selection, estimates of genetic variance from A-AM were also significantly overestimated when the effect of genomic selection was strong. Our results suggest that VC estimates from H-AM under random genotyping have the expected values. Predicted breeding values from H-AM were inflated when VC estimates were biased, and inflation differed between genotyped and ungenotyped animals, which can lead to suboptimal selection decisions.

Conclusions: We conclude that VC estimates from H-AM are biased with selective genotyping, but are close to expected values with random genotyping.VC estimates from A-AM in populations under genomic selection are also biased but to a much lesser degree. Therefore, we recommend the use of H-AM with random genotyping to estimate VC for populations under genomic selection. Our results indicate that it is still possible to use selective genotyping in selection, but then VC estimation should avoid the use of genotypes from one side only of the distribution of phenotypes. Hence, a dual genotyping strategy may be needed to address both selection and VC estimation.
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http://dx.doi.org/10.1186/s12711-020-00550-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291515PMC
June 2020

Correction to: A bivariate genomic model with additive, dominance and inbreeding depression effects for sire line and three-way crossbred pigs.

Genet Sel Evol 2020 05 6;52(1):23. Epub 2020 May 6.

SEGES, Danish Pig Research Centre, Danish Agriculture & Food Council F.m.b.A., Axelborg, Axeltorv 3, 1609, Copenhagen V, Denmark.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12711-020-00541-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204057PMC
May 2020

Reduced Myocardial Perfusion Reserve in Type 2 Diabetes Is Caused by Increased Perfusion at Rest and Decreased Maximal Perfusion During Stress.

Diabetes Care 2020 06 19;43(6):1285-1292. Epub 2020 Mar 19.

Department of Cardiology and Endocrinology, Slagelse Hospital, Region Zealand, Denmark.

Objective: To examine differences in myocardial blood flow (MBF) at rest and during stress between patients with type 2 diabetes and control subjects, and to identify potential predictors of changes in MBF at rest and during stress.

Research Design And Methods: A cross-sectional study was conducted of 193 patients with type 2 diabetes and 20 age- and sex-matched control subjects. Cardiovascular magnetic resonance was used to evaluate left ventricular structure and function and MBF at rest and during adenosine-induced stress. MBF was derived as the mean of the flow within all segments of a midventricular slice.

Results: Patients with type 2 diabetes had higher global MBF at rest (0.81 ± 0.19 mL/min/g) and lower global MBF during stress (2.4 ± 0.9 mL/min/g) than control subjects (0.61 ± 0.11 at rest, 3.2 ± 0.8 mL/min/g under stress; both < 0.01). Patients with macroalbuminuria had lower MBF during stress (1.6 ± 0.5 mL/min/g) than did patients with microalbuminuria (2.1 ± 0.7 mL/min/g; = 0.04), who in turn had lower MBF during stress than did normoalbuminuric patients (2.7 ± 0.9 mL/min/g; < 0.01). Patients with severe retinopathy had lower MBF during stress (1.8 ± 0.6 mL/min/g) than patients with simplex retinopathy (2.3 ± 0.7 mL/min/g; < 0.05) and those who did not have retinopathy (2.6 ± 1.0 mL/min/g; < 0.05). Albuminuria and retinopathy were associated with reduced MBF during stress in a multiple regression analysis. Stress-related MBF inversely correlated with myocardial extracellular volume ( < 0.001; = 0.37), a measure of diffuse myocardial fibrosis. A trend toward lower basal MBF was observed in patients treated with sodium-glucose cotransporter 2 inhibitors ( = 0.07).

Conclusions: Patients with type 2 diabetes have higher global MBF at rest and lower maximal MBF during vasodilator-induced stress than control subjects. Reduced MBF during stress is associated with diabetes complications (albuminuria and retinopathy) and is inversely correlated with diffuse myocardial fibrosis.
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http://dx.doi.org/10.2337/dc19-2172DOI Listing
June 2020

The predictive ability of indirect genetic models is reduced when culled animals are omitted from the data.

Genet Sel Evol 2020 Feb 10;52(1). Epub 2020 Feb 10.

SEGES, Danish Pig Research Centre, Danish Agriculture & Food Council F.m.b.A., Axelborg, Axeltorv 3, 1609, Copenhagen V, Denmark.

Background: Physical removal of individuals from groups causes reductions in group sizes and changes in group composition, which may affect the predictive ability of estimates of indirect genetic effects of animals on phenotypes of group mates. We hypothesized that including indirect genetic effects of culled animals and of animals without phenotypes in the analysis affects estimates of genetic parameters, improves predictive ability, and reduces bias of predicted breeding values. We tested this by applying different editing procedures, i.e. omission of individuals or groups from the data, and genetic models, i.e. a classical and an indirect genetic model (IGM) without or with weighting of indirect genetic effects based on the relative proportion of time spent in the pen or space allowance. Data consisted of average daily gain for 123,567 pigs in 11,111 groups, from which 3% of individuals in 25% of groups were prematurely removed from the group.

Results: The estimate of total heritability was higher (0.29 to 0.34) than that of direct heritability (0.23 to 0.25) regardless of the editing procedures and IGM used. Omission of individuals or groups from the data reduced the predictive ability of estimates of indirect genetic effects by 8 to 46%, and the predictive ability of estimates of the combined direct and indirect genetic effects by up to 4%. Omission of full groups introduced bias in predicted breeding values. Weighting of indirect genetic effects reduced the predictive ability of their estimates by at least 19% and of the estimates of the combined direct and indirect genetic effects by 1%.

Conclusions: We identified significant indirect genetic effects for growth in pigs. Culled animals should neither be removed from the data nor accounted for by weighting their indirect genetic effects in the model based on the relative proportion of time spent in the pen or space allowance, because it will reduce predictive ability and increase bias of predicted breeding values. Information on culled animals is important for prediction of indirect genetic effects and must be accounted for in IGM analyses by including fixed regressions based on relative time spent within the pen or relative space allowance.
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http://dx.doi.org/10.1186/s12711-020-0527-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011392PMC
February 2020

Bias in estimates of variance components in populations undergoing genomic selection: a simulation study.

BMC Genomics 2019 Dec 9;20(1):956. Epub 2019 Dec 9.

Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, DK-8830, Tjele, Denmark.

Background: After the extensive implementation of genomic selection (GS), the choice of the statistical model and data used to estimate variance components (VCs) remains unclear. A primary concern is that VCs estimated from a traditional pedigree-based animal model (P-AM) will be biased due to ignoring the impact of GS. The objectives of this study were to examine the effects of GS on estimates of VC in the analysis of different sets of phenotypes and to investigate VC estimation using different methods. Data were simulated to resemble the Danish Jersey population. The simulation included three phases: (1) a historical phase; (2) 20 years of conventional breeding; and (3) 15 years of GS. The three scenarios based on different sets of phenotypes for VC estimation were as follows: (1) Pheno: phenotypes from only the conventional phase (1-20 years); (2) Pheno: phenotypes from both the conventional phase and GS phase (1-35 years); (3) Pheno: phenotypes from only the GS phase (21-35 years). Single-step genomic BLUP (ssGBLUP), a single-step Bayesian regression model (ssBR), and P-AM were applied. Two base populations were defined: the first was the founder population referred to by the pedigree-based relationship (P-base); the second was the base population referred to by the current genotyped population (G-base).

Results: In general, both the ssGBLUP and ssBR models with all the phenotypic and genotypic information (Pheno) yielded biased estimates of additive genetic variance compared to the P-base model. When the phenotypes from the conventional breeding phase were excluded (Pheno), P-AM led to underestimation of the genetic variance of P-base. Compared to the VCs of G-base, when phenotypes from the conventional breeding phase (Pheno) were ignored, the ssBR model yielded unbiased estimates of the total genetic variance and marker-based genetic variance, whereas the residual variance was overestimated.

Conclusions: The results show that neither of the single-step models (ssGBLUP and ssBR) can precisely estimate the VCs for populations undergoing GS. Overall, the best solution for obtaining unbiased estimates of VCs is to use P-AM with phenotypes from the conventional phase or phenotypes from both the conventional and GS phases.
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http://dx.doi.org/10.1186/s12864-019-6323-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902321PMC
December 2019

Quantification of mitral valve regurgitation by 2D and 3D echocardiography compared with cardiac magnetic resonance a systematic review and meta-analysis.

Int J Cardiovasc Imaging 2020 Feb 29;36(2):279-289. Epub 2019 Oct 29.

Division of Cardiology, Department of Medicine, Glostrup University Hospital, Nordre Ringvej 54, Glostrup, 2600, Copenhagen, Denmark.

By means of systematic literature review and meta-analysis, we compared results of studies examining different echocardiographic methods assessing severity of mitral valve regurgitation volume (MVR) with cardiac magnetic resonance imaging (CMR) as standard reference. A systematic search of electronic databases revealed twenty studies eligible for meta-analysis. Results of 2D- and 3D-trans-thoracic (TTE) and trans-esophageal echocardiographic (TEE) proximal isovelocity surface area (PISA) and volumetric methods were compared with CMR. Mean differences (ml) with 95% limits of agreement (LoA) derived from Bland-Altman tests and correlations coefficients [(R) 95% confidence interval (CI)] were pooled together. Overall 1187 patients [mean age = 59 ± 13 years and 678(57%) males] with primary or secondary mild to severe MVR were included. Comparing all echocardiographic methods with CMR showed an overestimation and moderate agreement with difference and 95% LoA of 8.05(- 3.40, 19.49) ml, R = 0.73(95% CI 0.71-0.76) p < 0.001. 3D-PISA followed by 3D-volumetric methods showed the better agreement with an underestimation of - 3.20(- 12.33, 5.92) ml, R = 0.84(95% CI 0.78-0.89) p < 0.001 and overestimation of 3.73(- 9.17, 16.61) ml, R = 0.90(95% CI 0.87, 0.94) p < 0.001, respectively. 2D-volumetric method showed the poorest agreement with difference and 95% LoA of 23.56(- 4.19, 51.31) ml, R = 0.64(95% CI 0.54-0.73) p < 0.001. In patients (n = 280) with severe MVR, 2D technique incorrectly estimated regurgitation volume severity in 106 (38%) compared to 4(14%) patients using 3D technique. Among echocardiographic methods 3D-PISA agreed best with CMR as reference, making 3D-PISA the most reliable method to quantify MVR. CMR can be considered in severe MVR where uncertainties arise and a decision-making prior valve surgery is required. Further powerful studies are needed to assess the accuracy of different echocardiographic methods.
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http://dx.doi.org/10.1007/s10554-019-01713-7DOI Listing
February 2020

Cardiac perfusion, structure, and function in type 2 diabetes mellitus with and without diabetic complications.

Eur Heart J Cardiovasc Imaging 2020 08;21(8):887-895

Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200 Slagelse, Denmark.

Aims: Coronary microvascular disease (CMD) is a known complication in type 2 diabetes mellitus (T2DM). We examined the relationship between diabetic complications, left ventricular (LV) function and structure and myocardial perfusion reserve (MPR) as indicators of CMD in patients with T2DM and control subjects.

Methods And Results: This was a cross-sectional study of 193 patients with T2DM and 25 controls subjects. Patients were grouped as uncomplicated diabetes (n = 71) and diabetes with complications (albuminuria, retinopathy, and autonomic neuropathy). LV structure, function, adenosine stress, and rest myocardial perfusion were evaluated by cardiovascular magnetic resonance. Echocardiography was used to evaluate diastolic function. Patients with uncomplicated T2DM did not have significantly different LV mass and E/e* but decreased MPR (3.8 ± 1.0 vs. 5.1 ± 1.5, P < 0.05) compared with controls. T2DM patients with albuminuria and retinopathy had decreased MPR (albuminuria: 2.4 ± 0.9 and retinopathy 2.6 ± 0.7 vs. 3.8 ± 1.0, P < 0.05 for both) compared with uncomplicated T2DM patients, along with significantly higher LV mass (149 ± 39 and 147 ± 40 vs. 126 ± 33 g, P < 0.05) and E/e* (8.3 ± 2.8 and 8.1 ± 2.2 vs. 7.0 ± 2.5, P < 0.05). When entered in a multiple regression model, reduced MPR was associated with increasing E/e* and albuminuria and retinopathy were associated with reduced MPR.

Conclusions: Patients with uncomplicated T2DM have reduced MPR compared with control subjects, despite equivalent LV mass and E/e*. T2DM patients with albuminuria or retinopathy have reduced MPR and increased LV mass and E/e* compared with patients with uncomplicated T2DM. E/e* and MPR are significantly associated after adjustment for age, hypertension, and LV mass, suggesting a link between CMD and cardiac diastolic function.

Clinical Trial Registration: https://www.clinicaltrials.org. Unique identifier: NCT02684331.
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http://dx.doi.org/10.1093/ehjci/jez266DOI Listing
August 2020

Genetic analysis on body weight at different ages in broiler chicken raised in commercial environment.

J Anim Breed Genet 2020 Mar 17;137(2):245-259. Epub 2019 Oct 17.

Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, Tjele, Denmark.

A multivariate model was developed and used to estimate genetic parameters of body weight (BW) at 1-6 weeks of age of broilers raised in a commercial environment. The development of model was based on the predictive ability of breeding values evaluated from a cross-validation procedure that relied on half-sib correlation. The multivariate model accounted for heterogeneous variances between sexes through standardization applied to male and female BWs differently. It was found that the direct additive genetic, permanent environmental maternal and residual variances for BW increased drastically as broilers aged. The drastic increase in variances over weeks of age was mainly due to scaling effects. The ratio of the permanent environmental maternal variance to phenotypic variance decreased gradually with increasing age. Heritability of BW traits ranged from 0.28 to 0.33 at different weeks of age. The direct genetic effects on consecutive weekly BWs had high genetic correlations (0.85-0.99), but the genetic correlations between early and late BWs were low (0.32-0.57). The difference in variance components between sexes increased with increasing age. In conclusion, the permanent environmental maternal effect on broiler chicken BW decreased with increasing age from weeks 1 to 6. Potential bias of the model that considered identical variances for sexes could be reduced when heterogeneous variances between sexes are accounted for in the model.
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http://dx.doi.org/10.1111/jbg.12448DOI Listing
March 2020

Cardiac function and incidence of unexplained myocardial scarring in patients with primary carnitine deficiency - a cardiac magnetic resonance study.

Sci Rep 2019 09 26;9(1):13909. Epub 2019 Sep 26.

Department of Medicine, The National Hospital, Tórshavn, Faroe Islands.

Primary carnitine deficiency (PCD) not treated with L-Carnitine can lead to sudden cardiac death. To our knowledge, it is unknown if asymptomatic patients treated with L-Carnitine suffer from myocardial scarring and thus be at greater risk of potentially serious arrhythmia. Cardiac evaluation of function and myocardial scarring is non-invasively best supported by cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). The study included 36 PCD patients, 17 carriers and 17 healthy subjects. A CMR cine stack in the short-axis plane were acquired to evaluate left ventricle (LV) systolic and diastolic function and a similar LGE stack to evaluate myocardial scarring and replacement fibrosis. LV volumes and ejection fraction were not different between PCD patients, carriers and healthy subjects. However, LV mass was higher in PCD patients with the severe homozygous mutation, c.95 A > G (p = 0.037; n = 17). Among homozygous PCD patients there were two cases of unexplained myocardial scarring and this is in contrast to no myocardial scarring in any of the other study participants (p = 0.10). LV mass was increased in PCD patients. L-carnitine supplementation is essential in order to prevent potentially lethal cardiac arrhythmia and serious adverse cardiac remodeling.
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http://dx.doi.org/10.1038/s41598-019-50458-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763485PMC
September 2019

Genetic parameters for body weight and different definitions of residual feed intake in broiler chickens.

Genet Sel Evol 2019 Sep 23;51(1):53. Epub 2019 Sep 23.

Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, 8830, Tjele, Denmark.

Background: The objectives of this study were to (1) simultaneously estimate genetic parameters for BW, feed intake (FI), and body weight gain (Gain) during a FI test in broiler chickens using multi-trait Bayesian analysis; (2) derive phenotypic and genetic residual feed intake (RFI) and estimate genetic parameters of the resulting traits; and (3) compute a Bayesian measure of direct and correlated superiority of a group selected on phenotypic or genetic residual feed intake. A total of 56,649 male and female broiler chickens were measured at one of two ages ([Formula: see text] or [Formula: see text] days). BW, FI, and Gain of males and females at the two ages were considered as separate traits, resulting in a 12-trait model. Phenotypic RFI ([Formula: see text]) and genetic RFI ([Formula: see text]) were estimated from a conditional distribution of FI given BW and Gain using partial phenotypic and partial genetic regression coefficients, respectively.

Results: Posterior means of heritability for BW, FI and Gain were moderately high and estimates were significantly different between males and females at the same age for all traits. In addition, the genetic correlations between male and female traits at the same age were significantly different from 1, which suggests a sex-by-genotype interaction. Genetic correlations between [Formula: see text] and [Formula: see text] were significantly different from 1 at an older age but not at a younger age.

Conclusions: The results of the multivariate Bayesian analyses in this study showed that genetic evaluation for production and feed efficiency traits should take sex and age differences into account to increase accuracy of selection and genetic gain. Moreover, for communicating with stakeholders, it is easier to explain results from selection on [Formula: see text] than selection on [Formula: see text], since [Formula: see text] is genetically independent of production traits and it explains the efficiency of birds in nutrient utilization independently of energy requirements for production and maintenance.
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http://dx.doi.org/10.1186/s12711-019-0494-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757393PMC
September 2019

A bivariate genomic model with additive, dominance and inbreeding depression effects for sire line and three-way crossbred pigs.

Genet Sel Evol 2019 Aug 19;51(1):45. Epub 2019 Aug 19.

SEGES Pig Research Centre, Axeltorv 3, 1609, Copenhagen V, Denmark.

Background: Crossbreeding is widely used in pig production because of the benefits of heterosis effects and breed complementarity. Commonly, sire lines are bred for traits such as feed efficiency, growth and meat content, whereas maternal lines are also bred for reproduction and longevity traits, and the resulting three-way crossbred pigs are used for production of meat. The most important genetic basis for heterosis is dominance effects, e.g. removal of inbreeding depression. The aims of this study were to (1) present a modification of a previously developed model with additive, dominance and inbreeding depression genetic effects for analysis of data from a purebred sire line and three-way crossbred pigs; (2) based on this model, present equations for additive genetic variances, additive genetic covariance, and estimated breeding values (EBV) with associated accuracies for purebred and crossbred performances; (3) use the model to analyse four production traits, i.e. ultra-sound recorded backfat thickness (BF), conformation score (CONF), average daily gain (ADG), and feed conversion ratio (FCR), recorded on Danbred Duroc and Danbred Duroc-Landrace-Yorkshire crossbred pigs reared in the same environment; and (4) obtain estimates of genetic parameters, additive genetic correlations between purebred and crossbred performances, and EBV with associated accuracies for purebred and crossbred performances for this data set.

Results: Additive genetic correlations (with associated standard errors) between purebred and crossbred performances were equal to 0.96 (0.07), 0.83 (0.16), 0.75 (0.17), and 0.87 (0.18) for BF, CONF, ADG, and FCR, respectively. For BF, ADG, and FCR, the additive genetic variance was smaller for purebred performance than for crossbred performance, but for CONF the reverse was observed. EBV on Duroc boars were more accurate for purebred performance than for crossbred performance for BF, CONF and FCR, but not for ADG.

Conclusions: Methodological developments led to equations for genetic (co)variances and EBV with associated accuracies for purebred and crossbred performances in a three-way crossbreeding system. As illustrated by the data analysis, these equations may be useful for implementation of genomic selection in this system.
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http://dx.doi.org/10.1186/s12711-019-0486-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701075PMC
August 2019

Use of Repeated Group Measurements with Drop Out Animals for Variance Component Estimation and Genetic Evaluation: A Simulation Study.

G3 (Bethesda) 2019 09 4;9(9):2935-2940. Epub 2019 Sep 4.

Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, Tjele 8830, Denmark and.

The efficiency of feed utilization plays an important role in animal breeding. However, measuring feed intake (FI) is costly on an individual basis under practical conditions. Using group measurements to model FI could be practically feasible and cost-effective. The objectives of this study were to develop a random regression model based on repeated group measurements with consideration of missing phenotypes caused by drop out animals. Focus is on variance components (VC) estimation and genetic evaluation, and to investigate the effect of group composition on VC estimation and genetic evaluation using simulated datasets. Data were simulated based on individual FI in a pig population. Each individual had measurement on FI at 6 different time points, reflecting 6 different weeks during the test period. The simulated phenotypes consisted of additive genetic, permanent environment, and random residual effects. Additive genetic and permanent environmental effects were both simulated and modeled by first order Legendre polynomials. Three grouping scenarios based on genetic relationships among the group members were investigated: (1) medium within and across pen genetic relationship; (2) high within group relationship; (3) low within group relationship. To investigate the effect of the drop out animals during test period, a proportion (15%) of animals with individual phenotypes was set as the drop out animals, and two drop out scenarios within each grouping scenario were assessed: (1) animals were randomly dropped out; (2) animals with lower phenotypes were dropped out based on the ranking at each time point. The results show that using group measurements yielded similar VCs estimates but with larger SDs compared with the corresponding scenario of using individual measurements. Compared to scenarios without drop out, similar VC estimates were observed when animals were dropped out randomly, whereas reduced VC estimates were observed when animals were dropped out by the ranking of phenotypes. Different grouping scenarios produced similar VC estimates. Compared to scenarios without drop out, there were no loss of accuracies of genetic evaluation for drop out scenarios. However, dropping out animals by the ranking of phenotypes produced larger bias of estimated breeding values compared to the scenario without dropped out animals and scenario of dropping out animals by random. In conclusion, with an optimized group structure, the developed model can properly handle group measurements with drop out animals, and can achieve comparable accuracy of genetic evaluation for traits measured at the group level.
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http://dx.doi.org/10.1534/g3.119.400484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723121PMC
September 2019

Recurrent event survival analysis predicts future risk of hospitalization in patients with paroxysmal and persistent atrial fibrillation.

PLoS One 2019 7;14(6):e0217983. Epub 2019 Jun 7.

Department of Cardiology, Hvidovre University Hospital, Copenhagen, Denmark.

Background: In patients with paroxysmal atrial fibrillation (PAF) or persistent atrial fibrillation (PeAF) symptom burden and fear of hospital readmission are major causes of reduced quality of life. We attempted to develop a prediction model for future atrial fibrillation hospitalization (AFH) risk in PAF and PeAF patients including all previously experienced AFHs in the analysis, as opposed to time to first event.

Methods: Recurrent event survival analysis was used to model the impact of past AFHs on the risk of future AFHs. A recurrent event was defined as a hospitalization due to a new episode of AF. Death or progression to permanent AF were included as competing risks.

Results: We enrolled 174 patients with PAF or PeAF, mean follow up duration was 1279 days, and 325 AFHs were observed. Median patient age was 63.0 (IQR 52.2-68.0), 29% had PAF, and 71% were male. Highly significant predictors of future AFH risk were PeAF (HR 3.20, CI 2.01-5.11) and number of past AFHs observed (HR for 1 event: 2.97, CI 2.04-4.32, HR for ≥2 events: 7.54, CI 5.47-10.40).

Conclusion: In PAF and PeAF patients, AF type and observed AFH frequency are highly significant predictors of future AFH risk. The developed model enables risk prediction in individual patients based on AFH history and baseline characteristics, utilizing all events experienced by the patient. This is the first time recurrent event survival analysis has been used in AF patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217983PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555511PMC
February 2020
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