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Twin Research and Human Genetics : the... Dec 2019Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16,...
Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1-12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.
Topics: Biomedical Research; Diseases in Twins; Humans; Registries; Twin Studies as Topic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 31937381
DOI: 10.1017/thg.2019.121 -
Advances in Experimental Medicine and... 2020Genomic predisposition fails to fully explain the onset of complex diseases, which is well illustrated by the largely incomplete concordance among monozygotic twins.... (Review)
Review
Genomic predisposition fails to fully explain the onset of complex diseases, which is well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and non-coding RNA, are the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. Autoimmune diseases now include almost 100 conditions and are estimated to cumulatively affect up to 5% of the world population with a healthcare expenditure superior to cancer worldwide. Many advances in medicine have been made to treat these conditions but there are still gaps, and an innovative and efficient therapy is needed. Systemic autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, polymyositis, and dermatomyositis. Monozygotic twins discordant for any disease offer an ideal study design as they are matched for many factors, including genetic variation and this is a real advantage for epigenetics study. We will herein discuss the available data in the epigenetic differences leading to disease discordance in MZ twins for systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.
Topics: Autoimmune Diseases; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Inflammation; Twin Studies as Topic; Twins, Monozygotic
PubMed: 32445092
DOI: 10.1007/978-981-15-3449-2_3 -
BMC Psychology Jan 2022In the general population, 10.6% of people favor their left hand over the right for motor tasks. Previous research suggests higher prevalence of atypical (left-, mixed-,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the general population, 10.6% of people favor their left hand over the right for motor tasks. Previous research suggests higher prevalence of atypical (left-, mixed-, or non-right-) handedness in (i) twins compared to singletons, and in (ii) monozygotic compared to dizygotic twins. Moreover, (iii) studies have shown a higher rate of handedness concordance in monozygotic compared to dizygotic twins, in line with genetic factors playing a role for handedness.
METHODS
By means of a systematic review, we identified 59 studies from previous literature and performed three sets of random effects meta-analyses on (i) twin-to-singleton Odds Ratios (21 studies, n = 189,422 individuals) and (ii) monozygotic-to-dizygotic twin Odds Ratios (48 studies, n = 63,295 individuals), both times for prevalence of left-, mixed-, and non-right-handedness. For monozygotic and dizygotic twin pairs we compared (iii) handedness concordance Odds Ratios (44 studies, n = 36,217 twin pairs). We also tested for potential effects of moderating variables, such as sex, age, the method used to assess handedness, and the twins' zygosity.
RESULTS
We found (i) evidence for higher prevalence of left- (Odds Ratio = 1.40, 95% Confidence Interval = [1.26, 1.57]) and non-right- (Odds Ratio = 1.36, 95% Confidence Interval = [1.22, 1.52]), but not mixed-handedness (Odds Ratio = 1.08, 95% Confidence Interval = [0.52, 2.27]) among twins compared to singletons. We further showed a decrease in Odds Ratios in more recent studies (post-1975: Odds Ratio = 1.30, 95% Confidence Interval = [1.17, 1.45]) compared to earlier studies (pre-1975: Odds Ratio = 1.90, 95% Confidence Interval = [1.59-2.27]). While there was (ii) no difference between monozygotic and dizygotic twins regarding prevalence of left- (Odds Ratio = 0.98, 95% Confidence Interval = [0.89, 1.07]), mixed- (Odds Ratio = 0.96, 95% Confidence Interval = [0.46, 1.99]), or non-right-handedness (Odds Ratio = 1.01, 95% Confidence Interval = [0.91, 1.12]), we found that (iii) handedness concordance was elevated among monozygotic compared to dizygotic twin pairs (Odds Ratio = 1.11, 95% Confidence Interval = [1.06, 1.18]). By means of moderator analyses, we did not find evidence for effects of potentially confounding variables.
CONCLUSION
We provide the largest and most comprehensive meta-analysis on handedness in twins. Although a raw, unadjusted analysis found a higher prevalence of left- and non-right-, but not mixed-handedness among twins compared to singletons, left-handedness was substantially more prevalent in earlier than in more recent studies. The single large, recent study which included birth weight, Apgar score and gestational age as covariates found no twin-singleton difference in handedness rate, but these covariates could not be included in the present meta-analysis. Together, the secular shift and the influence of covariates probably make it unsafe to conclude that twinning has a genuine relationship to handedness.
Topics: Birth Weight; Functional Laterality; Humans; Prevalence; Twins, Dizygotic; Twins, Monozygotic
PubMed: 35033205
DOI: 10.1186/s40359-021-00695-3 -
Clinical Obstetrics and Gynecology Dec 2023Monoamniotic twins comprise a rare subset of twins at risk of unique and serious complications. In addition to the risks faced by all twins (premature birth, growth...
Monoamniotic twins comprise a rare subset of twins at risk of unique and serious complications. In addition to the risks faced by all twins (premature birth, growth restriction), all monochorionic twins (twin-to-twin transfusion syndrome), and all monozygotic twins (congenital anomalies), monoamniotic twins face the unique risk of cord entanglement, in addition to a markedly increased risk of congenital anomalies. Early diagnosis, screening for fetal anomalies and surveillance for twin-twin transfusion syndrome are critical. After fetal viability, frequent fetal monitoring reduces the risk of intrauterine fetal demise.
Topics: Female; Humans; Pregnancy; Pregnancy, Twin; Twins, Monozygotic
PubMed: 37910073
DOI: 10.1097/GRF.0000000000000817 -
Postgraduate Medical Journal Jan 2020
Topics: Ethical Analysis; Gene-Environment Interaction; Humans; Twin Studies as Topic; Twins, Monozygotic
PubMed: 31831594
DOI: 10.1136/postgradmedj-2019-137194 -
Twin Research and Human Genetics : the... Apr 2020The classical twin design relies on a number of strong number of assumptions in order to yield unbiased estimates of heritability. This includes the equal environments... (Review)
Review
The classical twin design relies on a number of strong number of assumptions in order to yield unbiased estimates of heritability. This includes the equal environments assumption - that monozygotic and dizygotic twins experience similar degrees of environmental similarity - an assumption that is likely to be violated in practice for many traits of interest. An alternative method of estimating heritability that does not suffer from many of these limitations is to model trait similarity between sibling pairs as a function of their empirical genome-wide identity by descent sharing, estimated from genetic markers. In this review, I recount the story behind Nick Martin's and my development of this method, our first attempts at applying it in a human population and more recent studies using the original and related methods to estimate trait heritability.
Topics: Genetic Markers; History, 20th Century; History, 21st Century; Humans; Twin Studies as Topic; Twins; Twins, Dizygotic; Twins, Monozygotic
PubMed: 32423516
DOI: 10.1017/thg.2020.21 -
Cold Spring Harbor Perspectives in... Jun 2021In this review, we discuss how samples comprising monozygotic and dizygotic twin pairs can be used for the purpose of strengthening causal inference by controlling for... (Review)
Review
In this review, we discuss how samples comprising monozygotic and dizygotic twin pairs can be used for the purpose of strengthening causal inference by controlling for shared influences on exposure and outcome. We begin by briefly introducing how twin data can be used to inform the biometric decomposition of population variance into genetic, shared environmental, and nonshared environmental influences. We then discuss how extensions to this model can be used to explore whether associations between exposure and outcome survive correction for shared etiology (common causes). We review several analytical approaches that can be applied to twin data for this purpose. These include multivariate structural equation models, cotwin control methods, direction of causation models (cross-sectional and longitudinal), and extended family designs used to assess intergenerational associations. We conclude by highlighting some of the limitations and considerations that researchers should be aware of when using twin data for the purposes of interrogating causal hypotheses.
Topics: Disease; Environmental Exposure; Humans; Twins, Dizygotic; Twins, Monozygotic
PubMed: 32900702
DOI: 10.1101/cshperspect.a039552 -
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 -
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 -
Obstetrics and Gynecology Clinics of... Mar 2020With an increasing incidence of twin gestations, understanding the inherent risks associated with these pregnancies is essential in modern obstetrics. The unique... (Review)
Review
With an increasing incidence of twin gestations, understanding the inherent risks associated with these pregnancies is essential in modern obstetrics. The unique differences in placentation in twins contribute to the increased risks. Monochorionic twins are susceptible to complications because of their unique placental architecture, including twin-to-twin transfusion syndrome, the twin anemia-polycythemia sequence, selective intrauterine growth restriction, and the twin reversed arterial perfusion sequence. Knowing the clinical correlations of placental anatomy in these gestations helps perinatal pathologists perform a more informed placental evaluation, allowing for better care for the mother and her children.
Topics: Female; Fetofetal Transfusion; Humans; Placenta; Pregnancy; Pregnancy, Twin; Twins, Monozygotic; Ultrasonography, Prenatal
PubMed: 32008674
DOI: 10.1016/j.ogc.2019.10.010