| 1. |
- Stamouli, S, et al.
(författare)
-
Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders
- 2018
-
Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 21:1, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.
|
|
| 2. |
- Arora, M., et al.
(författare)
-
Fetal and postnatal metal dysregulation in autism
- 2017
-
Ingår i: Nat Commun. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
|
|
| 3. |
- Bolte, S., et al.
(författare)
-
The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
- 2014
-
Ingår i: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:3, s. 164-176
-
Tidskriftsartikel (refereegranskat)abstract
- Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
|
|
| 4. |
- Willfors, C., et al.
(författare)
-
On the role of non-shared environment for executive functioning in ADHD: a twin-differences design study
- 2014
-
Ingår i: International Journal of Developmental Disabilities. - : Informa UK Limited. - 2047-3869 .- 2047-3877. ; 60:3, s. 163-173
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The study of differences between monozygotic (MZ) twin pairs with respect to ADHD may provide novel leads to disentangle the environmental contribution driving its phenotypes. Objectives: To examine non-shared environmental influences on executive function in dimensionally defined ADHD. Methods: This study included 27 MZ twin pairs (7 female) aged 11-20 years being moderately to substantially discordant for ADHD traits as assessed by the Attention Problem (AP) scale of the Child Behavior Checklist/Adult Behavior Checklist. The twins completed the Wisconsin Card Sorting Test (WCST) for cognitive flexibility and the Tower Test (TT) for foresighted planning. Two statistical approaches were used to analyze the data. First, correlations between ADHD trait intra-pair differences and WCST and TT scores were calculated. Second, the significance of those intra-pair differences on WCST and TT, using ADHD as categorical variable in clinically discordant pairs, was tested. Results: Both analysing strategies revealed a link between ADHD on one hand, and foresighted planning and inhibitory control on the other hand mediated by non-shared environmental factors. The first statistical approach yielded positive correlations between intra-pairs differences on the AP scale and intra-pair differences on two subscales of the TT: total rule violation (r(s)=0.41) and rule-violation-per-item-ratio (r(s)=0.38). Findings in categorically discordant pairs were consistent, showing within-pair differences on the same subtests (z-1.63, P=0.05, one-tailed and z=-1.60, P=0.05, one-tailed). Conclusions: Findings confirm previous research suggesting ADHD to be a quantitative extreme on a continuum with executive functions being a cognitive marker of ADHD traits. Non-shared environmental factors appear to influence planning skills and inhibitory control.
|
|
| 5. |
|
|
| 6. |
- Pan, P. Y., et al.
(författare)
-
Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder
- 2023
-
Ingår i: Molecular Autism. - 2040-2392. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAutism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD.MethodsIn this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities.ResultsSimilar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r(a)) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r(a) = 0.31), functional diarrhea (r(a) = 0.27) as well as mixed gastrointestinal disorders (r(a) = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r(a) = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r(a) = 0.30, 0.17, and 0.17, respectively).LimitationsImportantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits.ConclusionsShared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.
|
|
| 7. |
|
|
