The physiological benefits of vigorous exercise are well established. The existence of psychological benefits is less clear, however, due to methodological limitations common to investigatory studies. Two of these limitations are the difficulty of establishing appropriate control groups and the large variety of highly specific measures of psychological function available for consideration of effects. To address these limitations, we identified 63 pairs of monozygotic twins from the National Survey of Midlife Development in the United States who were discordant for the amount of vigorous exercise in which they engaged regularly. The twins who regularly engaged in vigorous exercise experienced greater positive psychological functioning than their nonexercising co-twins as measured by the latent factor representing the variance common to 8 measures of mood, optimism, control over life, and interpersonal aspects of personality. The magnitude of the difference was in excess of .4 standard deviations.

The Missouri Mothers and Their Children Study (MO-MATCH) was specifically designed to critically investigate prenatal environmental influences on child attention problems and associated learning and cognitive deficits. The project began as a pilot study in 2004 and was formally launched in 2008. Participants in the study were initially identified via the Department of Vital Statistics birth record (BR) database. Interview and lab-based data were obtained from: (1) mothers of Missouri-born children (born 1998–2005), who smoked during one pregnancy but not during another pregnancy; (2) biological fathers when available; and (3) the children (i.e., full sibling pairs discordant for exposure to maternal smoking during pregnancy (SDP). This within-mother, between-pregnancy contrast provides the best possible methodological control for many stable maternal and familial confounding factors (e.g., heritable and socio-demographic characteristics of the mother that predict increased probability of SDP). It also controls for differences between mothers who do and do not smoke during pregnancy, and their partners, that might otherwise artifactually create, or alternatively mask, associations between SDP and child outcomes. Such a design will therefore provide opportunities to determine less biased effect sizes while also allowing us to investigate (on a preliminary basis) the possible contribution of paternal or other second-hand smoke exposure during the pre, peri, and postnatal periods to offspring outcome. This protocol has developed a cohort that can be followed longitudinally through periods typically associated with increased externalizing symptoms and substance used initiation.

Nicotine and its primary oxidative metabolites are metabolized in part by glucuronidation. Genetic variation in UGT isoenzymes that catalyze glucuronidation activity suggests that variation in glucuronidation rate is in part genetically determined. The relative contribution of genetic and environmental sources to individual differences in the rate of glucuronidation of nicotine, cotinine, and trans-3'-hydroxycotinine was estimated in a twin study of nicotine pharmacokinetics. Glucuronidation rate was defined using measures that either accounted for variability in renal clearance or assumed the same relative renal clearance of parent drug and glucuronide conjugate across individuals. The former definition resulted in highly correlated nicotine and cotinine glucuronidation measures that were substantially influenced by the combined effect of additive (heritable) and non-additive (dominant and epistatic) genetic effects. These findings suggest that genetic variation in UGT isoenzymes that act in additive and interactive ways is an important determinant of individual variability in nicotine and cotinine metabolism via glucuronidation pathways.

The basis of most twin studies is the ascertainment of twins, often through twin registries, and determination of zygosity. The current rate of twin births in many industrialized countries implies that in the near future around 3% or more of individuals will be a twin. Hence, there are and will be a lot of twins around and many of those will not participate in twin studies. However, if large population-based samples are available that include appropriate identifiers, then twins can be detected and twin studies performed, even in the absence of zygosity information. We quantified the number of twin pairs that could be detected from a longitudinal survey in the Netherlands, which aims to answer questions about educational strategies and performance in primary education in the Netherlands. We detected 2865 twin pairs if we used a coded name identifier, date of birth, school, grade and year of survey, which is 2.01% of 284,945 pupils in five cohorts. Relaxing our selection criteria increased the number of apparent twin pairs identified, most of which are false positives due to chance matching of identification criteria. We show that the intraclass correlation on measured phenotypes can be used as a quality control measure for twin identification, and quantify the proportion of false negatives (true twin pairs not identified) due to missing data and data coding errors. We compared our estimated rate of twins in the sample to census data and estimate that with our most stringent selection criteria we detect more than 80% of all twin pairs in the sample. We conclude that the identification of twin pairs from large population-based samples is feasible, rapid and accurate if the appropriate identifiers are available, and that twin pairs from such sources are a valuable resource for studies to answer scientific question about twins versus nontwins and about genetic and environmental factors of twin resemblance.

Mothers of multiples who choose to feed their infants breast milk are faced with a seemingly overwhelming set of circumstances. Since mothers of multiples could potentially feed their infants differing proportions of breast milk, current methods of obtaining breastfeeding data for mothers of singletons may not adequately describe the breastfeeding behaviors of mothers of twins and triplets. The goal of our study was to determine the proportion of breast milk each infant of a multiple set was fed over a six-month period and compare the feeding regimens of sibling infants. Results of this retrospective study based on maternal reports indicated that there was almost complete agreement in the proportion of breast milk fed to siblings born from the same pregnancy, regardless of stratification based on gestational age, plurality, or location of the infants (hospital vs. home). The Pearson correlation coefficient for duration of breast-milk feeding between sibling twins was 0.99 (p < .0001); among sibling triplets the values were .97, .98 and .99 (p < .0001). A better understanding of the process by which twins and triplets are fed breast milk sets the stage for future research and can ultimately lead to the development of strategies to increase breast-milk feeding rates for multiple birth children.

More than 200 million children aged <5 years fail to reach their full cognitive potential, and children born as twins are particularly at risk. In this article, we review studies that examined differences in the neurodevelopmental outcomes of twins compared to singletons. We searched the Medline database for articles on twins, singletons, neuro, and cognitive development. We also inspected bibliographies of relevant publications to identify related articles from 2011 to 2017. Our search criteria yielded 162 studies, 8 of which met the inclusion criteria. Of the eight studies examined, four were prospective follow-up studies, three were cross-sectional studies, and one was a randomized controlled trial. Five of these studies were carried out in developed countries, and they found no statistically significant difference in neurodevelopmental outcomes among twins and singletons. However, two of the three studies carried out in developing countries found a difference with singletons having significantly higher academic ratings than twins. Studies in which neurodevelopmental outcomes were measured early in life (1–5 years) showed no significant twin–singleton differences, while those in which it was measured later in life showed mixed twin–singleton differences. Overall, these studies may have been underpowered and may not have been optimally designed and implemented. There is need for studies with adequate sample sizes, good design, and optimal measurement of all relevant covariates in order to resolve the conflicting reports in the literature.

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27–1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.

Using the continuous parameter estimation model (CPEM), a large genotyped adult sample of the population of Wisconsin, USA (the Wisconsin Longitudinal Study) is examined for evidence of the Scarr–Rowe effect, a gene × environment (G×E) interaction that reduces the heritability of IQ among those with low socioeconomic status (SES). This method allows the differential expressivity of polygenic scores predictive of both educational attainment and IQ (EA3) on the phenotype of IQ to be directly operationalized throughout the full range of these variables. Utilizing a parental SES factor-weighted composite as a measure of childhood SES, evidence for the Scarr–Rowe effect was found, that is, the genetic expressivity of EA3 on IQ increased with increasing parental SES (β = 0.08, p = 4.71×10−10, df = 6,255). The effect was found for both the male and female samples separately, β(males) = 0.08, p = 5.27×10−5, df = 3,018; β(females) = 0.08, p = 1.93×10−6, df = 3,236. The effects were furthermore robust to removing outlying values of parental SES and to log-transforming the SES variable. The results are similar to those produced using a more conventional two-way interaction model, with IQ predicting the EA3 × log of parental SES interaction after the main effects; however, CPEM allows for greater model degrees of freedom, thus is better powered to detect the effect when it is small in magnitude (CPEM β = 0.05, p = 6.69×10−5 vs. two-way interaction β = 0.02, pone-tailed = .045, in both models log parental SES is used).

The Osaka University Aged Twin Registry (OUATR) is the largest adult twin registry in Japan. Since its establishment in 1974, the OUATR has conducted a number of studies with particular focus on the environmental contribution to physical–cognitive–mental aging, longevity and aging-dependent diseases in later adulthood. The registry consists of 12,000 pairs of Japanese twins born between 1900 and 1935. Two hundred and fifty pairs of twins have undergone comprehensive medical examination to date. Follow-up questionnaires have been mailed out on a regular basis, for the purpose of checking current vital statuses, health conditions, and so forth. The main objective of this longitudinal twin study is to contribute to the prevention of lifestyle-related diseases and the promotion of successful aging.

The negative effects of very low birthweight on intellectual development have been well documented, and more recently this effect has been shown to generalise to birthweights within the normal range. In this study we investigate the etiology of this relationship by using a classical twin design to disentangle the contributions of genes and environment. A previous Dutch study (Boomsma et al., 2001) examining these effects indicated that genes were important in mediating the association of birthweight to full IQ measured at ages 7 and 10, but not at ages 5 and 12. Here the association between birthweight and IQ at age 16 is considered (N = 523 twin pairs). Using variance components modeling we found that the genetic variance in birthweight (4%) completely overlapped with that in verbal IQ but not performance or full IQ. Results further showed the importance of shared environmental effects on birthweight (~ 60%) but not on IQ (with genes explaining up to 72% of IQ variance). Models incorporating a direction of causation parameter between birthweight and IQ provided adequate fit to the data in either causal direction for performance and full IQ, but the model with verbal IQ causing birthweight was preferred to one in which birthweight influenced verbal IQ. As the measurement of birthweight precedes the measurement of twins' IQ at age 16, the influence of verbal IQ might be better considered as a proxy for parents' IQ or education, and it is possible that brighter mothers provide better prenatal environments for their children.

Background: Although the clinical importance of chorionicity in twin pregnancies has been studied widely, the significance of perinatal determination of zygosity using molecular genetic analyses remains controversial. The purpose of this study was to determine the frequency and clinical significance of twin gestations according to zygosity and chorionicity in a Korean population. Methods: We enrolled 569 women who delivered twin newborns (> 24 weeks) at Seoul National University Hospital between 1999 and 2008. Chorionicity was established by histologic examination of placentae. Zygosity was determined with sex of neonates, chorionicity, and DNA analysis of umbilical cord blood. Results: The frequency of dizygotic (DZ) twins was 71.0% (404/569 pairs) based on the opposite sex (238/404 [58.9%]) and DNA analyses (166/404 [41.1%]); that of monozygotic (MZ) twins was 29.0% (165/569), including monochorionic (MC) (72.1% [119/165]) and dichorionic (DC) twins (27.9% [46/165]), which was confirmed by DNA analyses. Among spontaneously conceived twins, the frequency of MZ twins was more than twice that of DZ twins. The risk of low birth weight was 1.8-fold higher among MZDC twins and 1.9-fold higher among MZMC twins than among DZDC twins (p < .05). Bronchopulmonary dysplasia occurred more frequently among MZMC twins than among DZDC twins (adjusted OR 8.42, 95% CI 1.82–39.08, p < .01). However, the frequencies of other neonatal morbidities were not significantly higher in the MZMC group than in the MZDC and DZDC groups. The perinatal mortality rate was 15 per 1000 total births in the DZDC twins, 20 per 1000 total births in the MZDC and 56 per 1000 total births in the MZMC (p < .01). Conclusions: Although monozygosity was shown to be a risk factor for perinatal death and accurate determination of zygosity plays a great role in the future consideration of organ transplantation and twin studies, the value of zygosity determination along with chorionicity in relation to overall neonatal morbidity was not definite.

Attempts have been made to identify factors influencing the sex ratio at birth (number of males per 100 females). Statistical analyses have shown that comparisons between sex ratios demand large data sets. The secondary sex ratio has been believed to vary inversely with the frequency of prenatal losses. This hypothesis suggests that the ratio is highest among singletons, medium among twins and lowest among triplets. Birth data in Sweden for the period 1869–2004 showed that among live births the secondary sex ratio was on average 105.9 among singletons, 103.2 among twins and 99.1 among triplets. The secondary sex ratio among stillbirths for both singletons and twins started at a high level, around 130, in the 1860s, but approached live birth values in the 1990s. This trend is associated with the decrease and convergence of stillbirth rates among males and females. For detailed studies, we considered data for Sweden in 1869–1878 and in 1901–1967. Marital status or place of residence (urban or rural) had no marked influence on the secondary sex ratio among twins. For triplets, the sex ratio showed large random fluctuations and was on average low. During the period 1901–1967, 20 quadruplet, two quintuplet and one sextuplet set were registered. The sex ratio was low, around 92.0.

Background: Though multiple policies have been implemented, the cigarette control in China is still facing a great challenge. At the same time, alcohol drinking has increasingly become a public health problem. Considering cigarette smoking and alcohol drinking often co-occur, a few studies tested the covariance of these phenotypes. However, the genetic and environmental correlation between them among Chinese population has not been determined. The main aim of this study is to fill this gap. Methods: From the Chinese National Twin Registry, we obtained the data on cigarette smoking and alcohol drinking behaviors. The ordinal bivariate genetic analysis was performed to fit the categorical variables. After identifying the best decomposition among the Cholesky, common, and independent pathway model, we established the most parsimonious submodel. Results: The correlation between current tobacco and alcohol use could be explained by Cholesky model. The shared environmental variances for both phenotypes were dropped to construct the most parsimonious submodel. Furthermore, the most parsimonious submodel showed a moderate correlation (0.32, 95%CI = 0.17 – 0.46) between the genetic components and a negligible non-shared environmental correlation. Conclusion: As the first bivariate genetic analysis on current tobacco smoking and current alcohol drinking in China, this study suggested a common genetic vulnerability to tobacco and alcohol use in male twins. Further studies should be carried out to track the pertinent genes that are related to the comorbidity of smoking and drinking in Chinese population. Another urgent need is to recognize the behavior-specific environmental risk factors.

Low socioeconomic status (SES) has been established as a risk factor for poor mental health; however, the relationship between SES and mental health problems can be confounded by genetic and environmental factors in standard regression analyses and observational studies of unrelated individuals. In this study, we used a within-pair twin design to control for unmeasured genetic and environmental confounders in investigating the association between SES and psychological distress. We also employed within–between pair regression analysis to assess whether the association was consistent with causality. SES was measured using the Index of Relative Socio-economic Disadvantage (IRSD), income and the Australian Socioeconomic Index 2006 (AUSEI06); psychological distress was measured using the Kessler 6 Psychological Distress Scale (K6). Data were obtained from Twins Research Australia’s Health and Lifestyle Questionnaire (2014–2017), providing a maximum sample size of 1395 pairs. Twins with higher AUSEI06 scores had significantly lower K6 scores than their co-twins after controlling for shared genetic and environmental traits (βW [within-pair regression coefficient] = −0.012 units, p = .006). Twins with higher income had significantly lower K6 scores than their co-twins after controlling for familial confounders (βW = −0.182 units, p = .002). There was no evidence of an association between the IRSD and K6 scores within pairs (βW, p = .6). Using a twin design to eliminate the effect of potential confounders, these findings further support the association between low SES and poor mental health, reinforcing the need to address social determinants of poor mental health, in addition to interventions targeted to individuals.

Aim: To determine the differences in hemoglobin (Hb) levels in the first 2 days after birth in uncomplicated monochorionic twins in relation to birth order and mode of delivery. Methods: All consecutive uncomplicated monochorionic pregnancies with two live-born twins delivered at our center were included in this retrospective study. We recorded Hb levels at birth and on day 2, and analyzed Hb levels in association with birth order, mode of delivery, and time interval between delivery of twin 1 and 2. Results: A total of 290 monochorionic twin pairs were analyzed, including 171 (59%) twins delivered vaginally and 119 (41%) twins born by cesarean section (CS). In twins delivered vaginally, mean Hb levels at birth and on day 2 were significantly higher in second-born twins compared to first-born twins: 17.8 versus 16.1 g/dL and 18.0 versus 14.8 g/dL, respectively (p < .01). Polycythemia was detected more often in second-born twins (12%, 20/166) compared to first-born twins (1%, 2/166; p < .01). Hb differences within twin pairs delivered by CS were not statistically or clinically significant. We found no association between inter-twin delivery time intervals and Hb differences. Conclusions: Second-born twins after vaginal delivery have higher Hb levels and more often polycythemia than their co-twin, but not when born by CS.

A consistent finding from twin studies is that the environment shared by family members does not contribute to the variation in susceptibility to asthma. At the same time, it is known that environmental risk factors that are shared by family members are associated with the liability for asthma. We hypothesize that the absence of a main effect of shared environmental factors in twin studies can be explained by gene–environment interaction, that is, that the effect of an environmental factor shared by family members depends on the genotype of the individual. We explore this hypothesis by modeling the resemblance in asthma liability in twin pairs as a function of various environmental risk factors and test for gene–environment interaction. Asthma data were obtained by parental report for nearly 12,000 5-year-old twin pairs. A series of environmental risk factors was examined: birth cohort, gestational age, time spent in incubator, breastfeeding, maternal educational level, maternal smoking during pregnancy, current smoking of parents, having older siblings, and amount of child care outside home. Results revealed that being a boy, born in the 1990s, premature birth, longer incubator time, and child care outside home increased the risk for asthma. With the exception of premature birth, however, none of these factors modified the genetic effects on asthma. In very premature children shared environmental influences were important. In children born after a gestation of 32 weeks or more only genetic factors were important to explain familial resemblance for asthma.

There is a growing body of literature linking religious attendance to prosocial behavior (PB). The main purposes of the present study were to estimate genetic and environmental influences on the frequency of religious attendance (FRA) and to explore whether and how FRA moderates genetic and/or environmental influences on PB. As part of the Nigerian Twin and Sibling Study, 2860 (280 monozygotic male, 417 monozygotic female, 544 dizygotic male, 699 dizygotic female, and 920 opposite-sex dizygotic) twins (mean age = 14.2 years; SD = 1.7 years; age range = 12–18 years) completed a questionnaire regarding FRA and a PB scale. Similar to the findings from western twin samples, FRA showed substantial shared environmental influences of 74% (95% CI = 69%, 78%), with absence of genetic effects. The phenotypic correlation between FRA and PB was modest but positive and significant (r = .12; p < .01), suggesting that PB is higher among more frequent attenders than among less frequent attenders. The results of gene–environment (G × E) interaction model-fitting analysis revealed that FRA changed individual environmental experiences rather than genetic effects on PB such that while genetic variance was stable, non-shared environmental variance declined, leading the total phenotypic variance of PB to decrease with increasing levels of religious attendance.

The Sri Lankan Twin Registry (SLTR), established in 1997, is a unique resource for twin and genetic research in a low- and middle-income country (LMIC). It comprises of a volunteer cohort of 14,120 twins (7,060 pairs) and 119 sets of triplets, and a population-based cohort of 19,040 (9,520 pairs) twins and 89 sets of triplets. Several studies have been conducted using this registry, including the Colombo Twin and Singleton Study (CoTaSS 1; 4,387 twins, 2,311 singletons), which have explored the prevalence and heritability of a range of psychiatric disorders as well as gene-environmental interplay. Currently, a follow-up study (CoTaSS 2) of the same cohort is underway, looking at the prevalence and interrelationship of key cardiovascular and metabolic risk markers (e.g., metabolic syndrome). A significant feature of CoTaSS 2 is the establishment of a biobank. Current SLTR work is extending beyond mental health and the interface between mental and physical health to new horizons, extending collaborations with the wider global twin research community. Ethics and governance have been given special emphasis in the initiative. Capacity building and public engagement are two crucial components. Establishment of a state-of-the-art genetic laboratory was a major accomplishment. SLTR is a classic showcase of successful North–South partnership in building a progressive research infrastructure in a LMIC.

We investigated the extent to which cognitive dysfunction is shaped by genetic or environmental influences, and whether these factors differ in women and men. All members of the Swedish Twin Registry aged 65 and older were screened by telephone using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those who scored poorly on the TELE. Data were available for 4308 pairs where both members responded and 5070 pairs where only one member was alive and participated. To analyze all available data, we used a raw data method extended to ordinal data. As the prevalence of cognitive dysfunction increases with age, we incorporated age-adjusted thresholds. The best fitting model from biometric analyses indicated 35% of the variation in liability to cognitive dysfunction could be explained by heritable influences and the remaining 65% by nonfamilial environmental influences. Differences by gender were not significant. As this is a normative population including cognitively intact individuals, preclinical dementia cases and demented individuals, the relative magnitude of genetic and environmental effects is of particular interest in light of high heritabilities found for dementias such as Alzheimer's disease. The findings emphasize the extent to which research is needed to uncover nonfamilial environmental influences on cognitive dysfunction in later life.

Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime ‘ever’ smoking measure was obtained from twins and relatives in the ‘Virginia 30,000’ sample and the ‘Australian 25,000’. Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI.