-
Sports Medicine - Open Dec 2017There is evidence for considerable heterogeneity in the responsiveness to regular physical activity (PA) which might reflect the influence of genetic factors. The aim of... (Review)
Review
BACKGROUND
There is evidence for considerable heterogeneity in the responsiveness to regular physical activity (PA) which might reflect the influence of genetic factors. The aim of this systematic review was to assess whether the response to a PA intervention for measures of body composition and cardiorespiratory fitness is (i) correlated within twin pairs and/or families and (ii) more correlated in monozygotic twins (MZ) compared to dizygotic twins (DZ), which would be consistent with genetic effects.
METHODS
We performed electronic database searches, combining key words relating to "physical activity" and "genetics", in MEDLINE, CINAHL, EMBASE, SPORTS Discuss, AMED, PsycINFO, WEB OF SCIENCE, and SCOPUS from the earliest records to March 2016. Twin and family studies were included if they assessed body composition and/or cardiorespiratory fitness following a PA intervention, and provided a heritability estimate, maximal heritability estimate, or within MZ twin pair correlation (r). Data on heritability (twin studies), maximal heritability (family studies), and the r were extracted from included studies, although heritability estimates were not reported as small sample sizes made them uninformative.
RESULTS
After screening 224 full texts, nine twin and five family studies were included in this review. The pooled r in response to PA was significant for body mass index (r = 0.69, n = 58), fat mass (r = 0.58, n = 48), body fat percentage (r = 0.55, n = 72), waist circumference (r = 0.50, n = 27), and VOmax (r = 0.39, n = 48), where "n" represents the total number of twin pairs from all studies. Maximal heritability estimates ranged from 0-21% for measures of body composition, and 22-57% for cardiorespiratory fitness. Twin studies differed in sample age, baseline values, and PA intervention, although the exclusion of any one study did not affect the results.
CONCLUSIONS
Shared familial factors, including genetics, are likely to be a significant contributor to the response of body composition and cardiorespiratory fitness following PA. Genetic factors may explain individual variation in the response to PA.
TRIAL REGISTRATIONS
PROSPERO Registration No CRD42015020056 .
PubMed: 28074345
DOI: 10.1186/s40798-016-0073-9 -
BMJ (Clinical Research Ed.) Sep 2016To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, and Cochrane databases (until December 2015).
REVIEW METHODS
Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks' gestation.
RESULTS
32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks' gestation (risk difference 1.2/1000, 95% confidence interval -1.3 to 3.6; I(2)=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I(2)=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (-12.4 to 17.4/1000; I(2)=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies.
CONCLUSIONS
To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks' gestation; in monochorionic pregnancies delivery should be considered at 36 weeks.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014007538.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care, Neonatal; Perinatal Death; Pregnancy; Pregnancy, Twin; Prospective Studies; Risk Factors; Stillbirth; Twins, Dizygotic; Twins, Monozygotic
PubMed: 27599496
DOI: 10.1136/bmj.i4353 -
Journal of Child Psychology and... May 2016The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.
METHODS
A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins.
RESULTS
The meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability.
CONCLUSIONS
We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.
Topics: Autism Spectrum Disorder; Diseases in Twins; Genetic Predisposition to Disease; Humans
PubMed: 26709141
DOI: 10.1111/jcpp.12499 -
Ultrasound in Obstetrics & Gynecology :... Aug 2014The aim of this systematic review was to explore the relationship between crown-rump length (CRL) discordance detected at 11-14 weeks of gestation and adverse outcome in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review was to explore the relationship between crown-rump length (CRL) discordance detected at 11-14 weeks of gestation and adverse outcome in twin pregnancy and to assess its predictive accuracy.
METHODS
A protocol designed a priori following MOOSE guidelines and recommended for systematic review and meta-analysis was used. The outcomes observed were: total fetal and perinatal loss, fetal loss at <24 weeks, fetal loss at ≥ 24 weeks, birth-weight (BW) discordance, preterm delivery (PTD) at < 34 weeks and fetal anomalies. The analysis was performed for all twins and for dichorionic (DC) and monochorionic (MC) twins separately.
RESULTS
A total of 2008 articles were identified and 17 studies were included in the systematic review. Twin pregnancies with CRL discordance ≥ 10% were at significantly higher risk of perinatal loss (RR, 2.80; 95% CI, 1.25-6.27; P = 0.012), fetal loss at ≥ 24 weeks (RR, 4.07; 95% CI, 1.47-11.23; P = 0.006), BW discordance (RR, 2.24; 95% CI, 1.89-2.64; P < 0.001) and PTD at < 34 weeks (RR, 1.49; 95% CI, 1.23-1.80; P < 0.001) but not of fetal loss at < 24 weeks (P = 0.130). A meta-analysis of fetal anomalies was not possible because fewer than two studies explored this outcome. However, when used alone to screen for adverse pregnancy outcome, the predictive accuracy of CRL discordance was low for each of the outcomes explored.
CONCLUSION
CRL discordance is associated with an increased risk of adverse pregnancy outcome. However, the accuracy of CRL discordance in predicting adverse outcome is poor and thus limits its routine use in clinical practice.
Topics: Birth Weight; Crown-Rump Length; Female; Fetus; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Pregnancy, Twin; Twins, Dizygotic; Twins, Monozygotic; Ultrasonography, Prenatal
PubMed: 24585501
DOI: 10.1002/uog.13335 -
Clinical Dysmorphology Oct 2012The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia,... (Review)
Review
The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. The identification of 14 twin pairs with an initial diagnosis of VATER/VACTERL association at our clinical centers led to the performance of a classical twin study. This involved a thorough evaluation of these 14 twin pairs and a further 55 twin pairs identified from a systematic review of the literature. The zygosity, concordance, and malformation status of all 69 twin pairs were evaluated. Twenty-four twin pairs fulfilled the criteria for inclusion in a comparison of the concordance rates between monozygous (MZ) and dizygous (DZ) twin pairs. The pairwise concordance rates were 15% [95% confidence interval (CI) 4-42%] for MZ and 18% (95% CI 5-48%) for DZ twin pairs (P=0.53). The probandwise concordance rates were 27% (95% CI 11-52%) for MZ and 31% (95% CI 13-58%) for DZ twin pairs (P=0.40). Although based on a limited number of twin pairs, the findings of the present study are consistent with the low number of familial cases reported to date, and suggest that the role of inherited genetic factors in the majority of VATER/VACTERL cases is limited.
Topics: Anus, Imperforate; Diseases in Twins; Esophagus; Heart Defects, Congenital; Humans; Radius; Spine; Trachea; Twins, Dizygotic; Twins, Monozygotic
PubMed: 22895008
DOI: 10.1097/MCD.0b013e328358243c -
Twin Research and Human Genetics : the... Feb 2012Cervical cancer is the third most common cancer in women worldwide. Persistent infection with an oncogenic human papillomavirus (HPV) is necessary, but not sufficient,... (Meta-Analysis)
Meta-Analysis
Cervical cancer is the third most common cancer in women worldwide. Persistent infection with an oncogenic human papillomavirus (HPV) is necessary, but not sufficient, for its development. Over many years, only a small proportion of women with chronic HPV infection progress to develop disease. The role of host genes and environmental factors in the pathogenesis of, or predisposition to, cervical cancer is still unclear. We conducted a systematic review of published literature in MEDLINE-PubMed to identify studies of cervical cancer susceptibility that used a twin study design. We used standard MeSH terms (controlled vocabulary) as well as specific free-text terms and combinations of terms related to cervical cancer, with no restriction on publication date. We performed a full text review to ensure the identified articles met our inclusion criteria and, if so, extracted information on demographics, sample size, study definitions, and key statistical findings. Of the 285 articles identified, three utilized a classical twin design and reported results specific to cervical cancer. The studies were based on cancer registry data from Scandinavia, with sample sizes ranging from 312 to 710 twin pairs. The findings from one study were consistent with a genetic mechanism for the causation of carcinoma in situ. Future research studies using the strength of the classic twin design, together with incorporation of HPV DNA status, are indicated to determine whether there is a potential role for genetic factors in the development of cervical cancer or high-grade cervical dysplasia from chronic oncogenic HPV infection.
Topics: Environment; Female; Humans; Medical Subject Headings; Papillomaviridae; Papillomavirus Infections; PubMed; Risk Factors; Scandinavian and Nordic Countries; Twins, Dizygotic; Twins, Monozygotic; United States; Uterine Cervical Neoplasms
PubMed: 22784457
DOI: 10.1375/twin.15.1.79 -
Genetic and epigenetic influences of twins on the pathogenesis of craniosynostosis: a meta-analysis.Plastic and Reconstructive Surgery Apr 2012The pathoetiology of craniosynostosis is not well understood. It likely results from a combination of genetic and epigenetic phenomena, such as intrauterine constraint... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pathoetiology of craniosynostosis is not well understood. It likely results from a combination of genetic and epigenetic phenomena, such as intrauterine constraint from multiple gestations. Information on craniosynostosis in twins is limited to case reports and series. The authors conducted a systematic review and meta-analysis of the literature to elucidate the genetic and nongenetic influences of twins on the pathogenesis of craniosynostosis.
METHODS
PubMed and Ovid databases were reviewed for the key terms "craniosynostosis and twins." Data analyzed included demographical information, incidence rates, concordance, and phenotypic variability. Risk factors for craniosynostosis, concordance, and phenotypic variability were assessed by univariate and multivariate analyses. A case series was presented.
RESULTS
Data were extracted from 34 journal articles, including the authors' five patients, and representing a total of 199 twins with craniosynostosis. Twinning was 2.62 times greater in patients with craniosynostosis (6.29 percent) compared with unaffected controls (2.4 percent; p < 0.0001). Boys were affected more than girls (65.30 versus 34.70 percent, respectively; p < 0.0001). Monozygotic concordance rates were greater than dizygotic (60.90 versus 5.30 percent, respectively; p < 0.0001) but were not 100 percent. Phenotypic variability was present in 62 percent of monozygotic twin sets (p < 0.05).
CONCLUSIONS
Increased concordance rates among monozygotic compared with dizygotic twins confirm the genetic role of twins on craniosynostosis. Evidence to support the epigenetic influence of twinning on the pathogenesis of craniosynostosis includes the elevated incidence of twins among a craniosynostotic population compared with unaffected twins in the general population and male gender predominance, as well as monozygotic phenotypic variability and discordance.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, IV.
Topics: Craniosynostoses; Diseases in Twins; Epigenesis, Genetic; Female; Humans; Infant; Male; Twins, Dizygotic; Twins, Monozygotic
PubMed: 22456364
DOI: 10.1097/PRS.0b013e31824422a8 -
European Journal of Epidemiology Apr 2012Increased body mass index (BMI) is a worldwide health issue. Individual differences in the susceptibility to increased BMI could be related to genes or environment. We... (Review)
Review
Increased body mass index (BMI) is a worldwide health issue. Individual differences in the susceptibility to increased BMI could be related to genes or environment. We performed a systematic review of genetic studies on BMI in pre-adolescence, young adulthood and late adulthood. We searched PubMed and EMBASE with heritability, body mass index, BMI, weight, height, anthropometry and twins as search terms. Studies reporting intra-pair correlations of healthy twin pairs that were raised together were included. This resulted in the inclusion of 8,179 monozygotic (MZ) and 9,977 dizygotic (DZ) twin pairs from twelve published studies in addition to individual participant data for 629 MZ and 594 DZ pairs from four twin registries. Structural equation modelling with intra-pair twin correlations showed that the heritability of BMI remained high over all age categories ranging from 61% (95% CI 54-64%) to 80% (95% CI 76-81%) for male and female subjects combined, while unique environmental influences increased from 14% (95% CI 13-15%) to 40% (95% CI 37-43%) with increasing age. Heritability of BMI remains consistently high over different age categories. Environmental changes over time do not seem to have as big a relative impact on an individual's weight as previously reported, suggesting a mainly genetic influence on variation in BMI over the years.
Topics: Body Composition; Body Mass Index; Body Weight; Child; Female; Humans; Male; Middle Aged; Obesity; Registries; Twins; Young Adult
PubMed: 22426805
DOI: 10.1007/s10654-012-9678-6 -
Birth Defects Research. Part A,... Mar 2012Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical... (Review)
Review
BACKGROUND
Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA.
METHODS
A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA.
RESULTS
The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs (p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs (p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively.
CONCLUSION
The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.
Topics: Diseases in Twins; Esophageal Atresia; Female; Genetic Predisposition to Disease; Humans; Male; Twins, Dizygotic; Twins, Monozygotic
PubMed: 22287212
DOI: 10.1002/bdra.22879 -
PloS One 2011Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect.
METHODS
We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data.
RESULTS
435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%.
CONCLUSIONS
Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.
Topics: Genetic Predisposition to Disease; Humans; Rheumatic Fever; Twin Studies as Topic; Twins, Dizygotic; Twins, Monozygotic
PubMed: 21980428
DOI: 10.1371/journal.pone.0025326