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Sonia Shah - One of the best experts on this subject based on the ideXlab platform.
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contribution of Genetic variation to transgenerational inheritance of dna methylation
Genome Biology, 2014Co-Authors: Allan F Mcrae, Joseph E Powell, Anjali K Henders, Lisa Bowdler, Gibran Hemani, Sonia ShahAbstract:Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The Genetic Heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the Heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations. The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to Genetic effects with any common environmental or zygotic effects being limited. The average Heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes. The majority of transgenerational similarity in DNA methylation is attributable to Genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.
Tim Cadman - One of the best experts on this subject based on the ideXlab platform.
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specific domains of early parenting their Heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
European Child & Adolescent Psychiatry, 2020Co-Authors: Iryna Culpin, Marc H. Bornstein, Diane L. Putnick, Hannah Sallis, Miguel Cordero, Priya Rajyaguru, Katarzyna Kordas, Ruby Lee, Tim CadmanAbstract:Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. This study describes different domains of early parenting behaviours and their Genetic Heritability, then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children and modelled as a latent factor using Confirmatory Factor Analysis. Genetic Heritability and correlations between parenting factors were estimated using genome-wide complex trait analysis. Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low Genetic Heritability. There was no evidence of association between parental enjoyment and offspring behavioural disorders and depressed mood. Stimulation was associated with better English grades (standardised β = 0.195, p < 0.001) and enjoyment was negatively associated with English grades (β = − 0.244, p = < 0.001). Conflictual relationships were associated with higher risk of offspring behavioural disorders (β = 0.228, p = 0.010) and depressed mood (β = 0.077, p = 0.005). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β = 0.113, p < 0.001). We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to the specificity of parenting domains and their long-term outcomes in children.
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specific domains of early parenting their Heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
bioRxiv, 2019Co-Authors: Iryna Culpin, Marc H. Bornstein, Diane L. Putnick, Hannah Sallis, Miguel Cordero, Priya Rajyaguru, Katarzyna Kordas, Ruby Lee, Tim CadmanAbstract:Abstract Background Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. The study describes different domains of early parenting behaviours, their Genetic Heritability, and then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Methods Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children, and modelled as a latent factor using Confirmatory Factor Analysis. Genetic Heritability and correlations between parenting factors were estimated using wide complex trait analysis. Offspring emotional, behavioural and academic outcomes were assessed at age 16 years using the self-reported Short Mood and Feelings Questionnaire, the Development and Well-Being Assessment, and grades achieved in national English Language examination. Results Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low Genetic Heritability. There was no evidence of associations between parenting factors and offspring depressed mood. Stimulation was associated with better English grades after controlling for maternal education (standardised β=0.058, p=0.007), and enjoyment was negatively associated with English grades (β=-0.082, p=0.002). Conflictual relationships were associated with higher risk of offspring behavioural disorders after controlling for behavioural problems at age 3 years (β=0.227, p=0.007). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β=0.113, p Conclusions We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to specificity of parenting domains and their long-term outcomes in children.
Claude Bouchard - One of the best experts on this subject based on the ideXlab platform.
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Findings from the Quebec Family Study on the Etiology of Obesity: Genetics and Environmental Highlights
Current Obesity Reports, 2014Co-Authors: Jean-philippe Chaput, Louis Perusse, Jean-pierre Després, Angelo Tremblay, Claude BouchardAbstract:The Quebec Family Study (QFS) was an observational study with three cycles of data collection between 1979 and 2002 in Quebec City, Canada. The cohort is a mixture of random sampling and ascertainment through obese individuals. The study has significantly contributed to our understanding of the determinants of obesity and associated disease risk over the past 35 years. In particular, the QFS cohort was used to investigate the contribution of familial resemblance and Genetic effects on body fatness and behaviors related to energy balance. Significant familial aggregation and Genetic Heritability were reported for total adiposity, fat-free mass, subcutaneous fat distribution, abdominal and visceral fat, resting metabolic rate, physical activity level and other behavioral traits. The resources of QFS were also used to study the contribution of several nontraditional (non-caloric) risk factors as predictors of excess body weight and gains in weight and adiposity over time, including low calcium and micronutrient intake, high disinhibition eating behavior trait, and short sleep duration. An important finding relates to the interactions between dietary macronutrient intake and exercise intensity on body mass and adiposity.
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Genetics of human obesity recent results from linkage studies
Journal of Nutrition, 1997Co-Authors: Claude BouchardAbstract:Excess body fat or body mass relative to height aggregates in families. It is commonly recognized that this familial aggregation of human obesity is accounted for in part by a significant Genetic component. Thus the Genetic Heritability of the obesity phenotypes accounts for ∼25-40% of the age- and gender-adjusted phenotypic variances. There is also growing evidence that single-gene effects can be detected under appropriate conditions. The focus of research has now shifted to candidate genes and DNA markers of various obesity phenotypes. To date, linkage results have been published from the Pima Indian Study, the San Antonio Family Heart or Diabetes Studies, the Paris Cohort of Obese Siblings, the University of Pennsylvania Family Obesity Study and the Quebec Family Study. The only genomic scan (with ∼600 markers) reported to date is that from the Pima Indian sibling study. In that study, the strongest evidence for linkage with body fat was with markers on chromosome 11q, 6p and 3p. Evidence for linkage with markers on 7q was obtained in all family studies with the only apparent exception being the Pima Indians. Our own results from the Quebec Family Study suggest that there are linkages between body fat, as assessed from hydrodensitometry, and markers on 1p32-p22. Other linkages have been reported in the past but they are generally based on smaller sample size and weaker evidence.
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familial aggregation of abdominal visceral fat level results from the quebec family study
Metabolism-clinical and Experimental, 1996Co-Authors: Louis Perusse, D. C. Rao, J P Despres, Simone Lemieux, Treva Rice, Claude BouchardAbstract:The purpose of this study was to investigate the importance of familial aggregation in abdominal visceral fat (AVF) level as assessed by computed tomography (CT). Four measures of abdominal adipose tissue, obtained from an abdominal scan between the fourth and fifth Lumbar vertebrae (L4-L5) taken in 366 adult subjects from 100 French-Canadian nuclear families, were considered in this study. Total abdominal fat, AVF, subcutaneous abdominal fat, obtained by computing the difference between total and AVF tissue areas, and the visceral to total abdominal fat ratio were measured. Spouses, parent-offspring, and sibling correlations were computed by maximum likelihood methods after adjustment of the four phenotypes for age and for age and total fat mass (FM) derived from underwater weighing. Significant familial aggregation was found for all phenotypes, whether adjusted or not for body FM. However, after adjustment of data for body FM, in addition to age, all spouse correlations became nonsignificant, suggesting that the familial aggregation of abdominal fat is primarily Genetic. Heritability estimates reached 42% and 56% for subcutaneous fat and AVF, respectively. These results suggest that Genetic factors are major determinants of the familial aggregation observed in the amount of abdominal fat, irrespective of total body fat content, and that AVF seems more influenced by Genetic factors than abdominal subcutaneous adipose tissue. These findings imply that some individuals are more at risk than others to exhibit the various metabolic complications associated with upper-body obesity because of their inherited tendency to store abdominal fat in the visceral depot rather than in the subcutaneous depot.
Katarzyna Kordas - One of the best experts on this subject based on the ideXlab platform.
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specific domains of early parenting their Heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
European Child & Adolescent Psychiatry, 2020Co-Authors: Iryna Culpin, Marc H. Bornstein, Diane L. Putnick, Hannah Sallis, Miguel Cordero, Priya Rajyaguru, Katarzyna Kordas, Ruby Lee, Tim CadmanAbstract:Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. This study describes different domains of early parenting behaviours and their Genetic Heritability, then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children and modelled as a latent factor using Confirmatory Factor Analysis. Genetic Heritability and correlations between parenting factors were estimated using genome-wide complex trait analysis. Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low Genetic Heritability. There was no evidence of association between parental enjoyment and offspring behavioural disorders and depressed mood. Stimulation was associated with better English grades (standardised β = 0.195, p < 0.001) and enjoyment was negatively associated with English grades (β = − 0.244, p = < 0.001). Conflictual relationships were associated with higher risk of offspring behavioural disorders (β = 0.228, p = 0.010) and depressed mood (β = 0.077, p = 0.005). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β = 0.113, p < 0.001). We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to the specificity of parenting domains and their long-term outcomes in children.
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specific domains of early parenting their Heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
bioRxiv, 2019Co-Authors: Iryna Culpin, Marc H. Bornstein, Diane L. Putnick, Hannah Sallis, Miguel Cordero, Priya Rajyaguru, Katarzyna Kordas, Ruby Lee, Tim CadmanAbstract:Abstract Background Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. The study describes different domains of early parenting behaviours, their Genetic Heritability, and then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Methods Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children, and modelled as a latent factor using Confirmatory Factor Analysis. Genetic Heritability and correlations between parenting factors were estimated using wide complex trait analysis. Offspring emotional, behavioural and academic outcomes were assessed at age 16 years using the self-reported Short Mood and Feelings Questionnaire, the Development and Well-Being Assessment, and grades achieved in national English Language examination. Results Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low Genetic Heritability. There was no evidence of associations between parenting factors and offspring depressed mood. Stimulation was associated with better English grades after controlling for maternal education (standardised β=0.058, p=0.007), and enjoyment was negatively associated with English grades (β=-0.082, p=0.002). Conflictual relationships were associated with higher risk of offspring behavioural disorders after controlling for behavioural problems at age 3 years (β=0.227, p=0.007). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β=0.113, p Conclusions We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to specificity of parenting domains and their long-term outcomes in children.
James L. N. Wood - One of the best experts on this subject based on the ideXlab platform.
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Heritability and epidemiology of canine hip dysplasia score and its components in labrador retrievers in the united kingdom
Preventive Veterinary Medicine, 2002Co-Authors: James L. N. Wood, K.h Lakhani, K RogersAbstract:Abstract Hip-dysplasia (malformation of the coxofemoral joint) in dogs is a major health problem. Under the British Veterinary Association/Kennel Club’s voluntary hip-dysplasia scheme, dog-owners/breeders submit radiographs from animals >1-year-old, to ensure adequate skeletal maturity. An overall hip score quantifies the degree of malformation in the hip joints of these animals, by summing the scores for nine components of the radiographs of both the left and right joints. The hip score data for 29,610 Labrador retrievers (registered with The Kennel Club, UK) were merged with the Kennel Club pedigree database for 472,435 Labrador retrievers. The merged data included the animal’s identity, date of birth, sex and hip score and similar records for the dog’s relatives, including the hip score if the relative had been tested. In recent years, breeding had been increasingly from tested parents. The mean hip score for male Labradors was significantly higher than that for females. Regression modelling showed a significant, positive dependence of the hip score of the offspring upon the hip scores of its sire, dam and grandparents. Genetic Heritability (using data from 13,382 Labrador retrievers comprising 718 litters) was highly significant: 0.34 from the two parents, 0.41 from sire alone and 0.30 from dam alone. Using components data from 2038 offspring Labrador retrievers comprising 1248 litters, three similar estimates of Heritability were significant for three major components (Norberg angle, cranial acetabular edge and subluxation); for other components, Heritability was significant from the sire but not from the dam. Offspring hip score could be reduced substantially by using only parents with zero hip score.
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Heritability and epidemiology of canine hip-dysplasia score in flat-coated retrievers and Newfoundlands in the United Kingdom.
Preventive veterinary medicine, 2000Co-Authors: James L. N. Wood, K.h Lakhani, R DennisAbstract:Hip dysplasia (malformation of the coxofemoral joint) in dogs is a major health problem for which the British Veterinary Association (BVA) had set up a control scheme in 1965. Based on scoring nine components of the radiographs of both the left and right joints, the degree of hip joint malformation is now quantified by an overall hip score (a measure of the condition of the hip joint). The hip scores of 1258 flat-coated retrievers and 1566 Newfoundlands (registered with The Kennel Club in the United Kingdom) were analysed after merging with Kennel Club pedigree data for 19036 flat-coated retrievers registered by 1995 and 14336 Newfoundlands registered by 1997. The merged data included the animal's identity, date of birth, sex and hip scores and also similar records for the dog's relatives including the hip score if the relative had been tested. In recent years, breeding has been increasingly from tested parents. There has been some reduction in offspring hip scores - presumably because breeders avoided breeding from males with very high scores. However, a much greater reduction in offspring hip score would be achieved by stricter science-based selection of potential sires and dams. Regression modelling quantified the positive relationship between offspring and parental hip scores. The Genetic Heritability of hip scores was large and significant in both breeds (particularly from dams). The breeders in UK tended to use healthy sires for breeding but they have taken less care in selecting dams. Our regression models emphasise the need for both sires and dams, particularly dams, to be healthy with very small hip scores.