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JAMA Jan 2016Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.
IMPORTANCE
Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.
OBJECTIVE
To estimate familial risk and heritability of cancer types in a large twin cohort.
DESIGN, SETTING, AND PARTICIPANTS
Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up.
EXPOSURES
Shared environmental and heritable risk factors among pairs of twins.
MAIN OUTCOMES AND MEASURES
The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death.
RESULTS
A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%).
CONCLUSIONS AND RELEVANCE
In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.
Topics: Aged; Aged, 80 and over; Denmark; Female; Finland; Follow-Up Studies; Gene-Environment Interaction; Humans; Incidence; Male; Neoplasms; Norway; Prospective Studies; Risk Assessment; Sweden; Time Factors; Twins, Dizygotic; Twins, Monozygotic
PubMed: 26746459
DOI: 10.1001/jama.2015.17703 -
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 -
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 -
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 -
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 -
European Spine Journal : Official... Jun 2012To estimate the heritability of scoliosis in the Swedish Twin Registry.
PURPOSE
To estimate the heritability of scoliosis in the Swedish Twin Registry.
METHODS
Self-reported data on scoliosis from 64,578 twins in the Swedish Twin Registry were analysed. Prevalence, pair- and probandwise concordances and tetrachoric correlations in mono- and dizygotic same-sex twins were calculated. The relative importance of genetic variance, i.e. the heritability, and unique and shared environmental variance was estimated using structural equation modelling in Mx software. In addition, all twins in the twin registry were matched against the Swedish Inpatient Register on the primary diagnosis idiopathic scoliosis.
RESULTS
The prevalence of scoliosis was 4%. Pair- and probandwise concordance was 0.11/0.17 for mono- and 0.04/0.08 for same-sex dizygotic twins. The tetrachoric correlation (95% CI) was 0.41 (0.33-0.49) in mono- and 0.18 (0.09-0.29) in dizygotic twins. The most favourable model in the Mx analyses estimated the additive genetic effects (95% CI) to 0.38 (0.18-0.46) and the unique environmental effects to 0.62 (0.54-0.70). Shared environmental effects were not significant. The pairwise/probandwise concordance for idiopathic scoliosis in the Swedish Inpatient Register was 0.08/0.15 for monozygotic and zero/zero for same-sex dizygotic twins.
CONCLUSION
Using self-reported data on scoliosis from the Swedish Twin Registry, we estimate that 38% of the variance in the liability to develop scoliosis is due to additive genetic effects and 62% to unique environmental effects. This is the first study of sufficient size to make heritability estimates of scoliosis.
Topics: Diseases in Twins; Female; Genetic Predisposition to Disease; Humans; Male; Prevalence; Registries; Scoliosis; Sweden; Twins, Dizygotic; Twins, Monozygotic
PubMed: 22094388
DOI: 10.1007/s00586-011-2074-1 -
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 -
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 -
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 -
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