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Purpose: Childhood incontinence is stigmatized and underprioritized, and a basic understanding of its pathogenesis is missing. Our goal was to identify risk-conferring genetic variants in daytime urinary incontinence (DUI)., Materials and Methods: We conducted a genome-wide association study in the Danish iPSYCH2015 cohort. Cases (3024) were identified through DUI diagnosis codes and redeemed prescriptions for DUI medication in individuals aged 5 to 20 years. Controls (30,240), selected from the same sample, were matched to cases on sex and psychiatric diagnoses, if any, and down-sampled to a 1:10 case:control ratio. Replication was performed in the Icelandic deCODE cohort (5475 cases/287,773 controls). Single-nucleotide polymorphism heritability was calculated using the genome-based restricted maximum likelihood method. Cross-trait genetic correlation was estimated using linkage disequilibrium score regression. Polygenic risk scores generated with LDpred2-auto and BOLT-LMM were assessed for association., Results: Variants on chromosome 6 (rs12210989, odds ratio [OR] 1.24, 95% CI 1.17-1.32, P = 3.21 × 10 -12 ) and 20 (rs4809801, OR 1.18, 95% CI 1.11-1.25, P = 3.66 × 10 -8 ) reached genome-wide significance and implicated the PRDM13 and RIPOR3 genes. Chromosome 6 findings were replicated ( P = .024, OR 1.09, 95% CI 1.01-1.16). Liability scale heritability ranged from 10.20% (95% CI 6.40%-14.00%) to 15.30% (95% CI 9.66%-20.94%). DUI and nocturnal enuresis showed positive genetic correlation ( r g = 1.28 ± 0.38, P = .0007). DUI was associated with attention-deficit/hyperactivity disorder (OR 1.098, 95% CI 1.046-1.152, P < .0001) and BMI (OR 1.129, 95% CI 1.081-1.178, P < .0001) polygenic risk., Conclusions: Common genetic variants contribute to the risk of childhood DUI, and genes important in neuronal development and detrusor smooth muscle activity were implicated. These findings may help guide identification of new treatment targets.

Background: The clinical impact of the functional CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression is not well studied. Here, we evaluate the utility of pharmacogenetic (PGx) testing in psychiatry by investigating the association between the phenotype status of the cytochrome P450 (CYP) 2C19/2D6 enzymes and the one-year risks of clinical outcomes in patients with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine. Methods: This study is a population-based cohort study of 17,297 individuals who were born between 1981 and 2005 with a depression diagnosis between 1996 and 2012. Using array-based single-nucleotide-polymorphism genotype data, the individuals were categorized according to their metabolizing status of CYP2C19/CYP2D6 as normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM). The outcomes were treatment switching or discontinuation, psychiatric emergency department contacts, and suicide attempt/self-harm. By using Poisson regression analyses, we have estimated the incidence rate ratios (IRR) with 95% confidence intervals (95% CI) that were adjusted for covariates and potential confounders, by age groups (<18 (children and adolescents), 19−25 (young adults), and 26+ years (adults)), comparing the outcomes in individuals with NM status (reference) versus the mutant metabolizer status. For statistically significant outcomes, we have calculated the number needed to treat (NNT) and the number needed to genotype (NNG) in order to prevent one outcome. Results: The children and adolescents who were using (es)citalopram with CYP2C19 PM status had increased risks of switching (IRR = 1.64 [95% CI: 1.10−2.43]) and suicide attempt/self-harm (IRR = 2.67 [95% CI; 1.57−4.52]). The young adults with CYP2C19 PM status who were using sertraline had an increased risk of switching (IRR = 2.06 [95% CI; 1.03−4.11]). The young adults with CYP2D6 PM status who were using fluoxetine had an increased risk of emergency department contacts (IRR = 3.28 [95% CI; 1.11−9.63]). No significant associations were detected in the adults. The NNG for preventing one suicide attempt/suicide in the children who were using (es)citalopram was 463, and the NNT was 11. Conclusion: The CYP2C19 and CYP2D6 PM phenotype statuses were associated with outcomes in children, adolescents, and young adults with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine, therefore indicating the utility of PGx testing, particularly in younger people, for PGx-guided antidepressant treatment.

Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could improve our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogenetic frequencies of genotypes and (combined) phenotypes of a large Danish population-based case-cohort sample (iPSYCH2012; data of the Integrative Psychiatric Research consortium). The genotyped sample consists of 77,684 individuals, of which 51,464 individuals had diagnoses of severe mental disorders (SMD case-cohort) and 26,220 were individuals randomly selected from the Danish population (population cohort). Array-based genotype data imputed to 8.4 million genetic variants was searched for a selected pharmacogenetic panel of 42 clinically relevant variants and a CYP2D6 gene deletion and duplication. We identified 19 of 42 variants. Minor allele frequencies (MAFs) were consistent with previously reported MAFs, and did not differ between SMD cases and population cohorts. Almost all individuals carried at least one genetic variant (> 99.9%) and 87% carried three or more genetic variants. When genotypes were translated into phenotypes, also > 99.9% of individuals had at least one divergent phenotype (i.e. divergent from the common phenotypes considered normal, e.g. extensive metabolizer). The high number of identified individuals with at least one pharmacogenetic variant or divergent phenotype indicates the importance of pharmacogenetic panel-based genotyping. Combined CYP2C19-CYP2D6 phenotypes revealed that 72.7% of individuals had divergent phenotypes for one or both enzymes. As CYP2D6 and CYP2C19 have an important role in the metabolism of psychotropic drugs, this indicates the relevance of pharmacogenetic testing specifically in individuals using psychotropic drugs.

Danish and European legislation recommend mink breeding programs that include selection for "confidence," defined as exploratory activity in a standardized behavioral test. Although this recommendation may improve mink welfare, farmers may consider this criterion risky due to possible negative consequences on other traits. The overall objectives of this study were to estimate the heritability of exploratory/fearful behavior and to identify genetic correlations with other traits of major economic importance in mink fur production. Various aspects of social influence on exploratory/fearful behavior, such as effects of the mother and litter siblings before weaning, the mother's age, and cage mates after weaning, were analyzed. In total, 26,371 1-yr-old Brown mink (Neovison vison) individuals born during the period of 2013 to2016 were included in the study. Exploratory/fearful behavior was the main trait analyzed. The production traits analyzed were live pelt quality and body weight. Both of these traits were assessed during live grading in November. Pelt length and quality were determined using the dried pelts of nonbreeders. Fertility data were obtained from the Fur Farm database. Linear mixed models were run using the restricted maximum-likelihood method. The genetic correlation between female and male behavior was 0.95 (SE = 0.06), indicating similar genetic backgrounds for both sexes (P = 0.40). For both sexes, the estimated heritability of behavior was 0.19 (SE = 0.03). We found no significant genetic correlation between behavior and production/fertility traits (P > 0.05). Common litter variance indicated a preweaning effect of litter mates and/or dam on postweaning temperament. There was a tendency for offspring from older mothers to explore more than offspring from 1-yr-old mothers. This trend was especially pronounced for males of 2-yr-old mothers (P = 0.05) and females of 4-yr-old mothers (P = 0.06). We conclude that confidence may be selected for among farm mink without detrimental effects on economically important production traits, such as pelt quality and fertility., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fur quality and skin size are integral qualities in the mink industry and are main determinants of sales price and subsequent income for mink fur producers. Parental animals of future generations are selected based on quality grading from live animals, but selection response is obtained from dried skins sold after pelting. In this study, we evaluated traits assessed during live grading and pelt traits examined on dried skins to determine correlation between live and pelt traits. Grading traits and body weight were measured during live animal grading for 9,539 Brown American mink, and pelt quality traits and skin size were evaluated on 8,385 dried mink skins after pelting. Data were sampled from 2 yearly production cycles. Genetic parameters were estimated using the REML method implemented in the DMU package. Heritabilities and proportions of litter variance were calculated from estimated variance components for all traits, and genetic and phenotypic correlations between all traits were estimated in a series of bivariate analyses. Heritability estimates for live grading traits ranged from 0.06 to 0.28, heritability estimates for pelt quality traits ranged from 0.20 to 0.30, and finally heritability estimates for body size traits ranged from 0.43 to 0.48. Skin size and body weight were regarded as different traits for the two sexes and were therefore analysed for each sex separately. Genetic correlations between grading traits exhibited a range of 0.30-0.99 and genetic correlations between pelt quality traits ranged from 0.38 to 0.86. Genetic correlations between quality, wool density and silky appearance evaluated during live animal grading and on dried skin after pelting were 0.74, 0.41 and 0.33, respectively. Skin size and body weight were negatively correlated with pelt quality traits and ranged from -0.55 to -0.25. Using standard selection index theory and combined information from both live grading and skin evaluation increase of reliability of selection ranged from 0.6% to 14%. Due to moderate genetic correlations between traits evaluated during live grading and on dried skins, and negative correlations between pelt quality traits and body size, we concluded that traits should be selected simultaneously., (© 2017 Blackwell Verlag GmbH.)

Feral American mink populations (), derived from mink farms, are widespread in Europe. In this study we investigated genetic diversity and genetic differentiation between feral and farm mink using a panel of genetic markers (194 SNP) generated from RAD sequencing data. Sampling included a total of 211 individuals from 14 populations, 4 feral and 10 from farms, the latter including a total of 7 color types (Brown, Black, Mahogany, Sapphire, White, Pearl, and Silver). Our study revealed similar low levels of genetic diversity in both farm and feral mink. Results are consistent with small effective population size as a consequence of line selection in the farms and founder effects of a few escapees from the farms in feral populations. Moderately high genetic differentiation was found between farm and feral animals, suggesting a scenario in which wild populations were founded from farm escapes a few decades ago. Currently, escapes and gene flow are probably limited. Genetic differentiation was higher among farm color types than among farms, consistent with line selection using few individuals to create the lines. Finally, no indications of inbreeding were found in either farm or feral samples, with significant negative values found in most farm samples, showing farms are successful in avoiding inbreeding.

This article documents the public availability of (i) RAD sequencing data and validated SNPs for the American mink Neovison vison and (ii) Transcriptome resources for two nonmodel freshwater crustacean species, the copepod Eucyclops serrulatus and the amphipod Echinogammarus veneris., (© 2015 John Wiley & Sons Ltd.)

Crosses between different mink lines from 3 Danish mink farms that use different breeding strategies were studied to estimate heterosis and variance components for litter size. The study was designed to analyze crosses between lines of the same color type, between different color types, and between animals originating from different farms. Effect of heterosis, color type, and variance components were estimated using Average information REML (AI-REML) algorithm implemented in the DMU package for analyzing multivariate mixed models. Females from 7 generations that gave birth to at least 1 offspring were analyzed and the effects of parity and production year were included in the analyses. Genetic trend and the proportions of the total variance explained by the effects of additive genetics (h2), common environment (due to repeated litters from the same female; c2), and dam of the female (granddame of the born litter; d2) were estimated. The results showed that mink of the Black color type potentially produced smaller litters compared to mink of the other studied color types. We found significant general maternal effect of heterosis for litter size. Analyses of specific heterosis showed a significant positive effect of crossing between lines of the same color type. Estimates of variance components revealed h2 levels for farm A, B, and C of 0.15, 0.06, and 0.09, respectively; thus litter size could be selected for in the future. The effect of common environment on litter size was also considerable, with c2 values of 0.005, 0.11, and 0.15 at farms A, B, and C, respectively. In conclusion, we recommend genetic selection as a means of increasing litter size in farmed mink.

Mapping of QTL affecting fur quality traits (guard hair length, guard hair thickness, density of wool, surface of the fur and quality) and skin length was performed in a three-generation mink population (F2 design). In the parental generation, Nordic Brown mink were crossed reciprocally with American Black short nap mink. In all, 1082 mink encompassing three generations were used for the analyses. The mink were genotyped for 104 microsatellites covering all 14 autosomes. The QTL analyses were performed by least-square regression implemented in gridqtl software. Genetic and phenotypic correlations and heritabilities were estimated using the average information-restricted maximum-likelihood method. Evidence was found for QTL affecting fur quality traits on nine autosomes. QTL were detected for guard hair thickness on chromosomes 1, 2, 3, 6 and 13; for guard hair length on chromosomes 2, 3 and 6; for wool density on chromosomes 6 and 13; for surface on chromosomes 7, 12 and 13; for quality on chromosomes 6, 7, 11 and 13; and for skin length on chromosomes 7 and 9. Proximity of locations of QTL for guard hair length, guard hair thickness and for wool density and quality suggests that some of the traits are in part under the influence of the same genes. Traits under the influence of QTL at close or identical positions also were traits that were strongly genotypically correlated. Based on the results of correlation analyses, the most important single traits influencing the quality were found to be density of wool, guard hair thickness and appearance of the surface., (© 2013 Stichting International Foundation for Animal Genetics.)

In this study, we performed a population viability analysis on 3 domestic horse breeds (Equus caballus) of Danish origin, namely, the Frederiksborg, the Knabstrupper, and the Jutland breeds. Because of their small population sizes, these breeds are considered endangered. The Vortex software simulation package was used for the population viability analysis. First, we investigated the future viability of these breeds based on present demographic and environmental parameters. Second, a sensitivity analysis revealed the most important variables for the viability of these breeds. Third, we examined management scenarios in which one of the studbooks was closed. According to the Vortex analysis, 2 of the breeds (Knabstrupper and Jutland) will persist for the next 200 yr, whereas the smaller breed (Frederiksborg) could become extinct within 40 yr. The sensitivity analyses indicated that the variables concerning reproduction of the mares had the greatest impact, with the number of mares actively breeding being the most influential on the population forecasts. The results suggest that closing the Knabstrupper studbooks can be done only if increasing the number of mares actively breeding counteracts the loss of genetic variation attributable to such a management strategy. It is recommended, based on these results, that the number of Frederiksborg and Knabstrupper mares actively breeding must be increased to approximately 30% in the 2 breeds that are presently using only 13%, while leaving the third (Frederiksborg ) at its present 30% level. Monitoring of the breeds in the future, however, may be exploited to adjust the breeding strategies. We suggest that the large amount of data required by Vortex makes it very useful for analyzing domestic animals because of the comprehensive data material often available. The results of this analysis accord with other studies on the Prezwalski horse, indicating robustness in the parameter sensitivity for horses.

A genetic analysis was performed on three indigenous Danish horse breeds using 12 microsatellite markers from a standard kit for parental testing. These three breeds are all considered endangered based on their small population sizes. Genetic variation in these three breeds was comparable to other horse breeds in Europe, and they do not seem to be at immediate danger of extinction caused by genetic deterioration. The Knabstrupper breed had more genetic variation, as measured by expected heterozygosity and allelic richness, than the other two breeds (Frederiksborg and Jutland). F(ST) statistics and population assignments confirmed population differentiation into three distinct breeds. The Frederiksborg and Knabstrupper breeds were closer to each other than to the Jutland breed. When establishing conservation priorities for the breeds, the priorities will depend on the conservation goals. Different methods for establishing conservation priorities are also discussed.