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Brain : a Journal of Neurology Mar 2020A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with...
A variety of cellular processes, including vesicle clustering in the presynaptic compartment, are impaired in Parkinson's disease and have been closely associated with α-synuclein oligomerization. Emerging evidence proves the existence of α-synuclein-related pathology in the peripheral nervous system, even though the presence of α-synuclein oligomers in situ in living patients remains poorly investigated. In this case-control study, we show previously undetected α-synuclein oligomers within synaptic terminals of autonomic fibres in skin biopsies by means of the proximity ligation assay and propose a procedure for their quantification (proximity ligation assay score). Our study revealed a significant increase in α-synuclein oligomers in consecutive patients with Parkinson's disease compared to consecutive healthy controls (P < 0.001). Proximity ligation assay score (threshold value > 96 using receiver operating characteristic) was found to have good sensitivity, specificity and positive predictive value (82%, 86% and 89%, respectively). Furthermore, to disclose the role of putative genetic predisposition in Parkinson's disease aetiology, we evaluated the differential accumulation of oligomers in a unique cohort of 19 monozygotic twins discordant for Parkinson's disease. The significant difference between patients and healthy subjects was confirmed in twins. Intriguingly, although no difference in median values was detected between consecutive healthy controls and healthy twins, the prevalence of healthy subjects positive for proximity ligation assay score was significantly greater in twins than in the consecutive cohort (47% versus 14%, P = 0.019). This suggests that genetic predisposition is important, but not sufficient, in the aetiology of the disease and strengthens the contribution of environmental factors. In conclusion, our data provide evidence that α-synuclein oligomers accumulate within synaptic terminals of autonomic fibres of the skin in Parkinson's disease for the first time. This finding endorses the hypothesis that α-synuclein oligomers could be used as a reliable diagnostic biomarker for Parkinson's disease. It also offers novel insights into the physiological and pathological roles of α-synuclein in the peripheral nervous system.
Topics: Autonomic Nervous System; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Immunoassay; Male; Middle Aged; Parkinson Disease; Presynaptic Terminals; Skin; Synucleins; Twins, Monozygotic
PubMed: 32025699
DOI: 10.1093/brain/awaa008 -
Twin Research and Human Genetics : the... Dec 2019The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth...
The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.
Topics: Aging; Biomedical Research; Child; Denmark; Diseases in Twins; Humans; Incidence; Longitudinal Studies; Registries; Twins, Dizygotic; Twins, Monozygotic
PubMed: 31544734
DOI: 10.1017/thg.2019.72 -
Journal of Assisted Reproduction and... Sep 2021The risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To...
Trend of medically induced monozygotic twin deliveries according to age, parity, and type of assisted reproductive technique during the period 2007-2017 in Lombardy Region, Northern Italy: a population-based study.
PURPOSE
The risk of monozygotic (MZT) twinning is increased in pregnancies after assisted reproductive technologies (ART). However, determinants remain poorly understood. To shed more light on this issue, we analyzed the estimated frequency of MZT twins from ART in Lombardy, Northern Italy, during the period 2007-2017.
METHODS
This is a population-based study using regional healthcare databases of Lombardy Region. After having detected the total number of deliveries of sex-concordant and sex-discordant twins from ART, we calculated MZT rate using Weinberg's method. Standardized ratios (SRs) and corresponding 95% confidence intervals (CI) of MZT deliveries, adjusted for maternal age, were computed according to calendar period, parity, and type of ART.
RESULTS
On the whole, 19,130 deliveries from ART were identified, of which 3,446 were twins. The estimated rate of MZT births among ART pregnancies was higher but decreased over time (p-value = 0.03); the SRs being 1.33 (95% CI: 1.18-1.51), 0.96 (95% CI: 0.83-1.11), and 0.92 (95% CI: 0.79-1.07) for the periods 2007-2010, 2011-2014, and 2015-2017, respectively. The SRs of MZT among women undergoing first-level techniques, conventional in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) were 0.47 (95% CI: 0.38-0.57), 1.02 (95% CI: 0.88-1.17), and 1.43 (95% CI: 1.27-1.61) (p-value < 0.0001). The ratio of MZT births was significantly higher in women younger than 35 years (p-value < 0.0001) and slightly higher among nulliparae (p-value < 0.0001).
CONCLUSION
Despite a reduction of MZT rate from ART over the time, the risk remains higher among ART pregnancies rather than natural ones. Younger women and women undergoing ICSI showed the highest risk of all.
Topics: Adolescent; Adult; Delivery, Obstetric; Embryo Transfer; Female; Fertilization in Vitro; Humans; Italy; Maternal Age; Middle Aged; Pregnancy; Pregnancy, Twin; Reproductive Techniques, Assisted; Sperm Injections, Intracytoplasmic; Time Factors; Twins, Monozygotic; Young Adult
PubMed: 34244872
DOI: 10.1007/s10815-021-02268-0 -
Behavior Genetics Jan 2024Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle-...
Nutrition and diet are key modifiable risk factors for the rising burden of non-communicable diseases like cardio-vascular diseases and diabetes in low- and middle- income countries (LMICs). The nutritional transition in dietary behaviours in LMICs has most likely contributed to this problem. Although traditionally assumed to be environmental, dietary choices are also genetically influenced. Twin study designs can be used to investigate the relative influence of genes and environment on nutrition intake, eating behaviours and associated psychological health. The overall aim of this project is to: provide proof-of-concept for the feasibility of using dietary (biomarker) data within the Children-of-Twin design in nutrition studies, develop laboratory skills and statistical genetic skills and establish a Sri Lankan-specific food composition database. Currently, a pilot study is being conducted with 304 individuals (38 Monozygotic twin pairs, 38 Dizygotic twin pairs and their male or female adult offspring). Questionnaire data on nutritional intake, eating behaviours, psychological well-being, physical health, and bio-specimens are being collected. A Sri Lankan-specific food composition database was developed, training sessions on macro and micro element analysis in biological samples and statistical genetics skills development were conducted and Community Engagement and Involvement programs were carried out in two districts of Sri Lanka.
Topics: Adult; Female; Humans; Male; Diseases in Twins; Feasibility Studies; Pilot Projects; Twins, Dizygotic; Twins, Monozygotic; Adult Children
PubMed: 38184818
DOI: 10.1007/s10519-023-10171-w -
International Journal of Environmental... Oct 2022Epidemiological studies have suggested the role of multiple genetic and environmental factors in the development of non-neoplastic gastrointestinal (GI) diseases;...
Comparison of Concordance of Peptic Ulcer Disease, Non-Adenomatous Intestinal Polyp, and Gallstone Disease in Korean Monozygotic and Dizygotic Twins: A Cross-Sectional Study.
Epidemiological studies have suggested the role of multiple genetic and environmental factors in the development of non-neoplastic gastrointestinal (GI) diseases; however, little information is available on these factors in the Korean population. Therefore, this cross-sectional study explored the effect of these factors by analyzing the concordance of several benign GI disorders in 525 monozygotic twins compared to that in 122 dizygotic twins aged >20 years from the Healthy Twin Study data of the Korean Genome and Epidemiology Study (2005-2014). Chi-square test, Wilcoxon rank-sum, and binomial and multinomial logistic regression models were used for statistical analysis. There was lack of concordance of gastric/duodenal ulcers and cholelithiasis/cholangitis between monozygotic twins compared to that in dizygotic twins, suggesting that environmental factors may mediate those concordant disease expressions in monozygotic twins. The concordance of intestinal polyps in monozygotic twins was 32% lower than that in dizygotic twins ( = 0.028), indicating that the effect of genetic factors on the risk for intestinal polyp development may be low. In conclusion, the lack or low concordance of several benign GI diseases between monozygotic and dizygotic twin groups suggests the relative importance of environmental factors, indicating that these are preventable diseases.
Topics: Cholelithiasis; Cross-Sectional Studies; Diseases in Twins; Humans; Intestinal Polyps; Peptic Ulcer; Republic of Korea; Twins, Dizygotic; Twins, Monozygotic
PubMed: 36232007
DOI: 10.3390/ijerph191912708 -
PloS One 2015Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own...
Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own faces from those of their co-twins has been scarcely investigated. One's own face is the most distinctive feature of the bodily self, and people typically show a clear advantage in recognizing their own face even more than other very familiar identities. Given the very high level of resemblance of their faces, monozygotic twins represent a unique model for exploring self-face processing. Herein we examined the ability of monozygotic twins to distinguish their own face from the face of their co-twin and of a highly familiar individual. Results show that twins equally recognize their own face and their twin's face. This lack of self-face advantage was negatively predicted by how much they felt physically similar to their co-twin and by their anxious or avoidant attachment style. We speculate that in monozygotic twins, the visual representation of the self-face overlaps with that of the co-twin. Thus, to distinguish the self from the co-twin, monozygotic twins have to rely much more than control participants on the multisensory integration processes upon which the sense of bodily self is based. Moreover, in keeping with the notion that attachment style influences perception of self and significant others, we propose that the observed self/co-twin confusion may depend upon insecure attachment.
Topics: Adolescent; Adult; Anxiety; Avoidance Learning; Emotions; Facial Recognition; Female; Humans; Male; Object Attachment; Twins, Monozygotic; Young Adult
PubMed: 25853249
DOI: 10.1371/journal.pone.0120900 -
Genome Biology Jan 2021Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such...
BACKGROUND
Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now.
RESULTS
We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue.
CONCLUSIONS
We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Genome, Human; Humans; Male; Middle Aged; Twins, Monozygotic; Young Adult
PubMed: 33402197
DOI: 10.1186/s13059-020-02223-9 -
Psychiatria Danubina Jun 2016
Topics: Adult; Delivery, Obstetric; Empathy; Female; Humans; Labor, Obstetric; Obstetric Labor, Premature; Pregnancy; Telepathy; Twins, Monozygotic
PubMed: 27287797
DOI: No ID Found -
Twin Research and Human Genetics : the... Jun 2015All same-sex dizygotic (DZ) twins and approximately one-third of monozygotic (MZ) twin pairs have separate placentas, making it impossible to use the number of placentas... (Comparative Study)
Comparative Study
All same-sex dizygotic (DZ) twins and approximately one-third of monozygotic (MZ) twin pairs have separate placentas, making it impossible to use the number of placentas to determine zygosity. Zygosity determination is further complicated because incorrect assumptions are often made, such as that only DZ pairs have two placentas and that all MZ pairs are phenotypically identical. These assumptions, by twins, their families and health professionals, along with the lack of universal zygosity testing for same-sex twins, has led to confusion within the twin community, yet little research has been conducted with twins about their understanding and assumptions about zygosity. We aimed to explore and quantify understanding and assumptions about zygosity using twins attending an Australian twin festival. We recruited 91 twin pairs younger than 18 years of age and their parents, and 30 adult twin pairs who were all uncertain of their zygosity, to complete one pen and paper questionnaire and one online questionnaire about their assumed zygosity, reasons for their assumptions and the importance of accurate zygosity knowledge. Responses were compared with their true zygosity measured using a genetic test. We found a substantial proportion of parents and twins had been misinformed by their own parents or medical professionals, and that knowledge of their true zygosity status provided peace of mind and positive emotional responses. For these reasons we propose universal zygosity testing of same-sex twins as early in life as possible and an increase in education of medical professionals, twins and families of twins about zygosity issues.
Topics: Adolescent; Adult; Aged; Attitude to Health; Child; Child, Preschool; Cohort Studies; DNA; Disclosure; Emotions; Exploratory Behavior; Female; Genotype; Human Rights; Humans; Infant; Male; Middle Aged; Parents; Patient Access to Records; Self Concept; Sibling Relations; Twins, Dizygotic; Twins, Monozygotic; Victoria; Young Adult
PubMed: 25851727
DOI: 10.1017/thg.2015.15 -
Cell Reports. Medicine Apr 2021Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and...
Tissue-specific mechanisms prompting obesity-related development complications in humans remain unclear. We apply multiomics analyses of subcutaneous adipose tissue and skeletal muscle to examine the effects of acquired obesity among 49 BMI-discordant monozygotic twin pairs. Overall, adipose tissue appears to be more affected by excess body weight than skeletal muscle. In heavier co-twins, we observe a transcriptional pattern of downregulated mitochondrial pathways in both tissues and upregulated inflammatory pathways in adipose tissue. In adipose tissue, heavier co-twins exhibit lower creatine levels; in skeletal muscle, glycolysis- and redox stress-related protein and metabolite levels remain higher. Furthermore, metabolomics analyses in both tissues reveal that several proinflammatory lipids are higher and six of the same lipid derivatives are lower in acquired obesity. Finally, in adipose tissue, but not in skeletal muscle, mitochondrial downregulation and upregulated inflammation are associated with a fatty liver, insulin resistance, and dyslipidemia, suggesting that adipose tissue dominates in acquired obesity.
Topics: Adipocytes; Adipose Tissue; Body Mass Index; Inflammation; Insulin Resistance; Mitochondria; Muscle, Skeletal; Obesity; Subcutaneous Fat; Twins, Monozygotic
PubMed: 33948567
DOI: 10.1016/j.xcrm.2021.100226