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Scientific Reports Jul 2022Individual differences in behaviour, traits and mental-health are partially heritable. Traditionally, studies have focused on quantifying the heritability of high-order...
Individual differences in behaviour, traits and mental-health are partially heritable. Traditionally, studies have focused on quantifying the heritability of high-order characteristics, such as happiness or education attainment. Here, we quantify the degree of heritability of lower-level mental processes that likely contribute to complex traits and behaviour. In particular, we quantify the degree of heritability of cognitive and affective factors that contribute to the generation of beliefs about risk, which drive behavior in domains ranging from finance to health. Monozygotic and dizygotic twin pairs completed a belief formation task. We first show that beliefs about risk are associated with vividness of imagination, affective evaluation and learning abilities. We then demonstrate that the genetic contribution to individual differences in these processes range between 13.5 and 39%, with affect evaluation showing a particular robust heritability component. These results provide clues to which mental factors may be driving the heritability component of beliefs formation, which in turn contribute to the heritability of complex traits.
Topics: Educational Status; Humans; Multifactorial Inheritance; Phenotype; Twins, Dizygotic
PubMed: 35821231
DOI: 10.1038/s41598-022-15492-0 -
Transfusion Aug 2018Chimeras are organisms composed of cells derived from two or more zygotes. Clinicians, blood group serologists, and cytogeneticists have recognized natural human... (Review)
Review
BACKGROUND
Chimeras are organisms composed of cells derived from two or more zygotes. Clinicians, blood group serologists, and cytogeneticists have recognized natural human chimeras for more than 60 years and molecular biologists are now able to recognize them using more sensitive and definitive tests.
STUDY DESIGN
Human chimeras are divided into two major classes, man-made and natural. Man-made chimeras include transplanted patients and several kinds of iatrogenic chimeras including those that develop after in vitro fertilization (IVF). Natural chimeras have historically included twin chimeras and fusion chimeras. Recently described microchimeras are primarily natural ones as well. Updated terminology and classification are suggested to account for information gleaned from natural and experimental animal chimeras.
CONCLUSIONS
Many human chimeras remain undetected. The states of health and disease of human chimeras remain largely unknown. Of four ways to detect human chimeras, molecular typing is the most sensitive and specific. Before systematic and temporal studies can be undertaken, improved cell sampling and better analytical detection methods are necessary. Chimeras may be sought among dizygotic twins and children born after IVF procedures.
Topics: Chimera; Fertilization in Vitro; Humans; Molecular Typing; Twins, Dizygotic
PubMed: 30153329
DOI: 10.1111/trf.14791 -
Behavior Genetics Jan 2019While a standard part of twin modeling, the magnitude of shared environment (c) is rarely examined by comparing estimates obtained using other methods. To clarify these...
While a standard part of twin modeling, the magnitude of shared environment (c) is rarely examined by comparing estimates obtained using other methods. To clarify these effects on familial resemblance, we estimated c for 20 diverse phenotypes in: (i) monozygotic and dizygotic twins, (ii) all step-siblings, and (iii) reared together and apart half-siblings, ascertained from the Swedish general population. The mean c estimates (± 95% CIs) differed across methods and were higher from twins (0.18; 0.13-0.23) than from the step (0.12; 0.09-0.14) and half-sibs (0.09; 0.06-0.13). c estimates correlated moderately across these three methods (ICC = + 0.28). When step-siblings from blended (each sib biologically related to one parent) and adoption-like families (one sib offspring of both parents and one of neither), were examined separately, resemblance was much lower in the latter. We need to clarify the range of environmental processes now considered together under the term "shared environment."
Topics: Computer Simulation; Environment; Female; Gene-Environment Interaction; Humans; Male; Models, Genetic; Parents; Phenotype; Siblings; Social Environment; Sweden; Twins; Twins, Dizygotic; Twins, Monozygotic
PubMed: 30536082
DOI: 10.1007/s10519-018-9940-0 -
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 -
Human Reproduction (Oxford, England) Jan 2024Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast,... (Meta-Analysis)
Meta-Analysis
Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins.
Topics: Female; Humans; Pregnancy; Fertilization; Genetic Association Studies; Retrospective Studies; Twins, Dizygotic; Twins, Monozygotic; Infant, Newborn
PubMed: 38052159
DOI: 10.1093/humrep/dead131 -
Journal of Attention Disorders Nov 2023We examined the characteristics and heritability of Autism Spectrum Disorder (ASD) and ADHD through a twin study.
OBJECTIVE
We examined the characteristics and heritability of Autism Spectrum Disorder (ASD) and ADHD through a twin study.
METHOD
Our sample included 44 twins, with at least one twin diagnosed with ASD. Among the participants, 30 had ASD, and 18 of them also had coexisting ADHD.
RESULTS
We observed higher concordance rates for ASD in monozygotic twins compared to dizygotic twins (67% vs. 25%), indicating a genetic influence on ASD. Inattentive symptoms of ADHD were more prevalent in monozygotic twins. The ASD + ADHD group exhibited significantly higher Social Responsiveness Scale scores, indicating greater social difficulties compared to the ASD and typical development groups. Twin analyses revealed that shared genetic factors accounted for 72.25% of the variance in both ASD and ADHD symptoms.
CONCLUSIONS
Our findings suggest that the comorbidity of ASD and ADHD may indicate increased severity and can be explained by shared genetic factors underlying both conditions.
Topics: Humans; Child; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Twins, Monozygotic; Twins, Dizygotic; Comorbidity
PubMed: 37480257
DOI: 10.1177/10870547231187166 -
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 -
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 -
JAMA Health Forum Jul 2021Wealthy adults tend to live longer than those with less wealth. However, a challenge in this area of research has been the reduction of potential confounding by factors...
IMPORTANCE
Wealthy adults tend to live longer than those with less wealth. However, a challenge in this area of research has been the reduction of potential confounding by factors associated with the early environment and heritable traits, which could simultaneously affect socioeconomic circumstances in adulthood and health across the life course.
OBJECTIVE
To identify the association between net worth at midlife and subsequent all-cause mortality in individuals as well as within siblings and twin pairs.
DESIGN SETTING AND PARTICIPANTS
This cohort study conducted a series of analyses using data from the Midlife in the United States (MIDUS) study, an ongoing national study of health and aging. The sample included adults (unrelated individuals, full siblings, and dizygotic and monozygotic twins) aged 20 to 75 years, who participated in wave 1 of the MIDUS study, which occurred from 1994 to 1996. The analyses were conducted between November 16, 2019, and May 18, 2021.
EXPOSURES
Self-reported net worth (total financial assets minus liabilities) at midlife (the middle years of life).
MAIN OUTCOMES AND MEASURES
All-cause mortality was tracked over nearly 24 years of follow-up, with a censor date of October 31, 2018. Survival models tested the association between net worth and all-cause mortality. Discordant sibling and twin analyses compared longevity within siblings and twin pairs who, given their shared early experiences and genetic backgrounds, were matched on these factors.
RESULTS
The full sample comprised 5414 participants, who had a mean (SD) age of 46.7 (12.7) years and included 2766 women (51.1%). Higher net worth was associated with lower mortality risk (hazard ratio [HR], 0.95; 95% CI, 0.94-0.97; < .001). Among siblings and twin pairs specifically (n = 2490), a similar within-family association was observed between higher net worth and lower mortality (HR, 0.94; 95% CI, 0.91-0.97; = .001), suggesting that the sibling or twin with more wealth tended to live longer than their co-sibling or co-twin with less wealth. When separate estimates were performed for the subsamples of siblings (HR, 0.94; 95% CI, 0.90-0.97; = .002), dizygotic twins (HR, 0.94; 95% CI, 0.86-1.02; = .19), and monozygotic twins (HR, 0.95; 95% CI, 0.87-1.04; = .34), the within-family estimates of the net worth-mortality association were similar, although the precision of estimates was reduced among twins.
CONCLUSIONS AND RELEVANCE
This cohort study found that wealth accumulation at midlife was associated with longevity in US adults. Discordant sibling analyses suggested that this association is unlikely to be simply an artifact of early experiences or heritable characteristics shared by families.
Topics: Adult; Aged; Cohort Studies; Female; Humans; Longevity; Longitudinal Studies; Male; Middle Aged; Social Class; Twins, Dizygotic; Twins, Monozygotic; United States; Young Adult
PubMed: 35977209
DOI: 10.1001/jamahealthforum.2021.1652 -
JAMA Psychiatry Jun 2024Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given...
IMPORTANCE
Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders.
OBJECTIVE
To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding.
DESIGN, SETTING, AND PARTICIPANTS
This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023.
EXPOSURES
A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey.
MAIN OUTCOMES AND MEASURES
Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register.
RESULTS
Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11).
CONCLUSIONS AND RELEVANCE
This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.
Topics: Humans; Adult; Female; Male; Adverse Childhood Experiences; Sweden; Middle Aged; Young Adult; Adolescent; Mental Disorders; Registries; Cohort Studies; Twins, Monozygotic; Twins, Dizygotic; Mental Health
PubMed: 38446452
DOI: 10.1001/jamapsychiatry.2024.0039