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Proceedings of the National Academy of... Jul 2005Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as... (Comparative Study)
Comparative Study
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
Topics: 5-Methylcytosine; Acetylation; Adult; Analysis of Variance; DNA Methylation; Electrophoresis, Capillary; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Histones; Humans; Male; Nucleic Acid Amplification Techniques; Oligonucleotide Array Sequence Analysis; Phenotype; Restriction Mapping; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Spain; Surveys and Questionnaires; Twins, Monozygotic; X Chromosome Inactivation
PubMed: 16009939
DOI: 10.1073/pnas.0500398102 -
Neuroscience and Biobehavioral Reviews May 2019Self-control is the ability to control one's impulses when faced with challenges or temptations, and is robustly associated with physiological and psychological... (Meta-Analysis)
Meta-Analysis Review
Self-control is the ability to control one's impulses when faced with challenges or temptations, and is robustly associated with physiological and psychological well-being. Twin studies show that self-control is heritable, but estimates range between 0% and 90%, making it difficult to draw firm conclusions. The aim of this study was to perform a meta-analysis to provide a quantitative overview of the heritability of self-control. A systematic search resulted in 31 included studies, 17 reporting on individual samples, based on a sample size of >30,000 twins, published between 1997 and 2018. Our results revealed an overall monozygotic twin correlation of 0.58, and an overall dizygotic twin correlation of 0.28, resulting in a heritability estimate of 60%. The heritability of self-control did not vary across gender or age. The heritability did differ across informants, with stronger heritability estimates based on parent report versus self-report or observations. This finding provides evidence that when aiming to understand individual differences in self-control, one should take genetic factors into account. Recommendations for future research are discussed.
Topics: Humans; Impulsive Behavior; Self Report; Self-Control; Twin Studies as Topic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 30822436
DOI: 10.1016/j.neubiorev.2019.02.012 -
Scandinavian Journal of Medicine &... Sep 2022Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations,... (Review)
Review
Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.
Topics: Adult; Exercise; Finland; Humans; Motor Activity; Physical Fitness; Twins, Monozygotic
PubMed: 35770444
DOI: 10.1111/sms.14205 -
Nature Mar 2022Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental...
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25-IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.
Topics: Genetic Predisposition to Disease; Humans; Interleukin-2; Multiple Sclerosis; OX40 Ligand; Twins, Dizygotic; Twins, Monozygotic
PubMed: 35173329
DOI: 10.1038/s41586-022-04419-4 -
Fertility and Sterility Jan 2010To study concordance rates of cryptorchidism (undescended testis) in pairs of boys with varying family structure, to evaluate the risk contribution from the intrauterine...
OBJECTIVE
To study concordance rates of cryptorchidism (undescended testis) in pairs of boys with varying family structure, to evaluate the risk contribution from the intrauterine environment and genetic factors.
DESIGN
Population based study of 1,024,500 Danish boys born from January 1, 1973 to December 31, 2004. Classic twin method and computerized square dance design.
SETTING
Hospitals and outpatient clinics.
PATIENT(S)
Six groups of boy pairs: boys with no relation, paternal half-brothers, maternal half-brothers, full brothers, dizygotic twin brothers, and monozygotic twin brothers.
INTERVENTION(S)
Observational study.
MAIN OUTCOME MEASURE(S)
Status on each individual regarding cryptorchidism and orchiopexy from the Danish National Patient Register.
RESULT(S)
Concordance rates of cryptorchidism in the groups were as follows: boys with no relation 3.2% (95% confidence interval 2.7%-3.6%), paternal half-brothers 3.4% (2.3%-4.7%), maternal half-brothers 6.0% (4.5%-7.7%), full brothers 8.8% (8.3%-9.8%), dizygotic twin brothers 24.1% (16.0%-33.6%), and monozygotic twin brothers 27.3% (15.5%-41.2%).
CONCLUSION(S)
The concordance rate was higher in maternal than in paternal half-brothers, and much higher but of equal magnitude in both twin groups. The findings strongly support that the intrauterine environment and maternal inheritance are contributing to the occurrence of cryptorchidism.
Topics: Adolescent; Adult; Child; Child, Preschool; Cryptorchidism; Denmark; Environment; Genetic Predisposition to Disease; Heredity; Humans; Logistic Models; Male; Odds Ratio; Orchiopexy; Pedigree; Registries; Risk Assessment; Risk Factors; Twins, Dizygotic; Twins, Monozygotic; Young Adult
PubMed: 19022430
DOI: 10.1016/j.fertnstert.2008.09.041 -
Sleep Health Oct 2021The causal nature of the sleep-obesity association is unclear. To control for potential confounding by genes and shared environment, we studied monozygotic twin pairs...
OBJECTIVES
The causal nature of the sleep-obesity association is unclear. To control for potential confounding by genes and shared environment, we studied monozygotic twin pairs discordant for body mass index (BMI). First, we investigated sleep in relation to BMI. Second, we examined associations of objective and subjective sleep duration and sleep debt (objective or subjective sleep duration minus subjective sleep need) with eating behaviors and physical activity (PA).
DESIGN
Cross-sectional study.
SETTING
Finnish twins in everyday life circumstances.
PARTICIPANTS
Seventy-four healthy young adult monozygotic twin pairs, of whom 36 were BMI-discordant (∆BMI ≥ 3 kg/m).
MEASUREMENTS
Clinical measurements estimated BMI and body composition. Sleep, eating, and PA behaviors were measured by self-report and actigraphy.
RESULTS
Compared to co-twins with lower BMI, co-twins with higher BMI reported shorter sleep (P = .043), more snoring (P = .0093), and greater tiredness (P = .0013) and trended toward eveningness (P = .036). Actigraphy-measured sleep duration correlated highly within BMI-discordant twin pairs (r = 0.63, P = .004). Subjective sleep debt was consistently positively associated with disinhibited eating and binge eating, but not with BMI. Subjective and objective sleep debt had negative correlations with moderate-to-vigorous PA.
CONCLUSIONS
Twins with higher BMI showed less favorable sleep characteristics than their co-twins with lower BMI. Subjective sleep debt is a potential target for intervention to reduce eating and PA behaviors that promote weight gain. Experimental studies could elucidate mechanisms underlying tiredness in individuals with higher BMI and investigate causal relationships between sleep debt, BMI, and lifestyle.
Topics: Body Mass Index; Cross-Sectional Studies; Humans; Life Style; Sleep; Twins, Monozygotic; Young Adult
PubMed: 34193396
DOI: 10.1016/j.sleh.2021.04.002 -
Twin Research and Human Genetics : the... Jun 2022In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a...
In this study, we analyzed the estimated frequency of monozygotic (MZ) and dizygotic (DZ) spontaneous twins in Lombardy during the period 2007-2017. This is a population-based study using the regional healthcare utilization databases of the Lombardy Region. The total number of spontaneous twin deliveries, in separate strata of like and unlike sex, was obtained. Moreover, estimates of DZ and MZ twin births were calculated using Weinberg's method. The standardized rates (SRs), adjusted for maternal age, of DZ and MZ twin births were computed according to calendar period. The twinning rates were calculated among strata of parity and maternal age. Finally, DZ:MZ ratio was calculated. Among the 734,278 spontaneous deliveries, 9176 (12.5 out of 1000 births) couples of twins were identified. In the three periods considered (i.e. 2007-2010, 2011-2014 and 2015-2017), no trend in the SRs of MZ twins was observed, respectively 0.41 (95% CI [0.40, 0.43]), 0.43 (95% CI [0.42, 0.45]) and 0.43 (95% CI[0.42, 0.45]). Differently, a slightly decreasing trend was observed in DZ twins SRs, respectively 0.87 (95% CI [0.84, 0.89]), 0.81 (95% CI [0.79, 0.83]), and 0.78 (95% CI [0.76, 0.80]). As concerns parity and maternal age, the rate of DZ twin births was consistently higher in nulliparae women aged 35 years or more. In our cohort, despite the increase of maternal age, a decline of spontaneous twin births emerged, especially due to the downward trend of DZ twins.
Topics: Adult; Female; Humans; Maternal Age; Pregnancy; Pregnancy, Twin; Twinning, Dizygotic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 35765814
DOI: 10.1017/thg.2022.19 -
Journal of Assisted Reproduction and... Apr 2023To determine the recurrence risk and risk factors for monozygotic splitting after elective single-embryo transfers (eSET).
PURPOSE
To determine the recurrence risk and risk factors for monozygotic splitting after elective single-embryo transfers (eSET).
METHODS
A retrospective cohort study was performed investigating 65,664 eSET cycles that resulted in a clinical pregnancy as reported in the Society for Assisted Reproductive Technology (SART) Clinical Outcomes Reporting System (CORS) between 2004 and 2017. Monozygosity was defined as more than one fetal heart tone by the first-trimester ultrasound and concordant sex at live birth. The primary outcome was recurrence risk, with recurrence defined as one patient having two or more cycles of eSET resulting in monozygotic multiples. The secondary objective was to identify factors associated with smonozygotic splitting, using a multivariable logistic regression model and a stepwise purposeful model selection.
RESULTS
There were 1355 (2.05%) pregnancies that resulted in two or more fetal heart tones after SET, including 840 monozygotic twins and triplets at birth. Recurrence occurred in two cases-0.0001% of patients with multiple eSET cycles. One case resulted from embryos created from a single cohort with intracytoplasmic sperm injection (ICSI), assisted hatching (AH), and blastocyst transfers. The second case resulted from donor egg embryos with ICSI and blastocyst transfers. Risk factors associated with monozygotic live birth were blastocyst transfer (OR 1.23, 95% CI 1.04-1.47, P = 0.0176) and AH (OR 1.23, 95% CI 1.05-1.44, P = 0.0081).
CONCLUSION
Recurrence of monozygotic live births in eSET was very rare. Blastocyst transfer and AH were confirmed to be risk factors for monozygotic live births, while ICSI, PGT, and FET do not appear to be associated.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Male; Twins, Monozygotic; Retrospective Studies; Fertilization in Vitro; Semen; Embryo Transfer; Risk Factors
PubMed: 36746891
DOI: 10.1007/s10815-023-02737-8 -
Genes Feb 2019Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if...
Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if zygosity matters. We investigate whether a possible difference in mortality after infancy between zygosities is stable in different age cohorts, and whether the difference remains when twins with unknown zygosity are taken into account. Further, we compare the distribution of long-livers, that is, the upper-tail of the lifespan distribution, between monozygotic and same-sex dizygotic twin individuals. The Danish Twin Registry provides a nationwide cohort of 109,303 twins born during 1870 to 1990 with valid vital status. Standard survival analysis is used to compare mortality in monozygotic and dizygotic twin individuals and twin individuals with unknown zygosity. The mortality of monozygotic and dizygotic twin individuals differs slightly after taking into consideration effects of birth- and age-cohorts, gender differences, and that twins are paired. However, no substantial nor systematic differences remain when taking twins with unknown zygosity into account. Further, the distribution of long-livers is very similar by zygosity, suggesting the same mortality process. The population-based and oldest twin cohort ever studied suggests that monozygotic and dizygotic twins have similar lifespans.
Topics: Adult; Aged; Denmark; Female; Humans; Longevity; Male; Middle Aged; Mortality; Registries; Twins, Dizygotic; Twins, Monozygotic
PubMed: 30791679
DOI: 10.3390/genes10020166 -
Fertility and Sterility Oct 2015To estimate the relative contribution of genetic influences and prevalence on endometriosis.
OBJECTIVE
To estimate the relative contribution of genetic influences and prevalence on endometriosis.
DESIGN
Analysis of self-reported data from a nationwide population-based twin registry.
SETTING
Not applicable.
PATIENT(S)
A total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006).
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Self-reported endometriosis, validated by medical records.
RESULT(S)
A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects.
CONCLUSION(S)
Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis.
Topics: Adult; Aged; Cross-Sectional Studies; Diseases in Twins; Endometriosis; Female; Genetic Predisposition to Disease; Humans; Middle Aged; Models, Genetic; Quantitative Trait, Heritable; Twins, Dizygotic; Twins, Monozygotic; Young Adult
PubMed: 26209831
DOI: 10.1016/j.fertnstert.2015.06.035