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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
The St. Louis aerosol was sampled during the period 16-22 August 1973 simultaneously at two locations using cascade impactors for sequential 12-hour samples. The six particle size fractions of each sampling were individually analyzed using PIXE for elements from S to Br and beyond and for heavy elements including Pb which permitted time variations of concentrations and particle size distributions to be followed and related to meteorological changes during the sampling period. In addition, the data were compared with average levels of the elements in coastal north Florida and maritime Bermuda as well as at a third St. Louis site. From this it appeared that some of the concentrations in St. Louis were at natural levels whereas others appeared to be higher and linked to air pollution sources. These relationships and others in this study may lead to criteria for distinguishing between pollutants and natural background in urban aerosols.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
We present some preliminary results of an optical and radio study of the very active RS CVn binary HD 127535. Photometric measurements show the presence of a large amplitude wave which exhibits marked changes in shape and range on time scales as short as a few months. This photometric variation is almost certainly due to large cool starspots on the cooler, more luminous component. As part of a survey of southern active-chromosphere stars with the Parkes radio telescope, HD 127535 has been observed at 5, 8.4 and 22 GHz. No detection was made at 5 GHz, possibly because of confusion due to the angular proximity of the star to the galatic plane. However, it is one of the strongest sources detected in the 8.4 GHz survey, and is one of only two stars detected at 22 GHz. Photometry obtained two cycles before the 8.4 GHz observations suggest a possible correlation between the radio emission and the photometric wave, i.e. spot visibility, but more data are needed.
We present the first massive frequency analysis of the 1200 first overtone RR Lyrae stars in the Large Magellanic Cloud observed in the first 4.3 yr of the MACHO project. Besides the many new double-mode variables, we also discovered stars with closely spaced frequencies. These variables are most probably nonradial pulsators.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses.
Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24–37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder.
Additive genetic (a2 = 0.48–0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a2 = 0.39) and shared environmental (c2 = 0.15) factors. All substance use disorders were influenced by shared genetic factors (rg = 0.38–0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40–73% of the genetic variance per substance.
Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
We used the winter of 2009–2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009–2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from −5% to −2%. For hospitalizations, errors ranged from −10% to −2% for pneumonia/influenza and from −3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.
It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD prevalence, symptomatology, and risk factors, and (2) genetic and/or environmental liability to MDD, we analyzed data from a large population-representative sample of twins ascertained from birth records (n = 550 AA and n = 3226 EA female twins) aged 18–28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (odds ratio = 0.88, 95% confidence interval [CI]: 0.67–1.15). Most MDD risk factors identified among AA women were also associated with MDD at similar magnitudes among EA women. Although the MDD heritability point estimate was higher among AA women than EA women in a model with paths estimated separately by race (56%, 95% CI: 29–78% vs. 41%, 95% CI: 29–52%), the best fitting model was one in which additive genetic and non-shared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33–53% and E = 57%, 47–67%). In spite of a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Many research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the course and outcome based on individual symptoms scores.
Data from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes.
LCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate–severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning.
The different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms.