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Objective: Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being., Methods: The twin subsample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (wave 1, 1995-1996; wave 2, 2004-2006). Only monozygotic twins (n = 713) were included in analyses. In separate multilevel models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1., Results: Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = 0.40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = 0.06, p = .02). Well-being was not a moderator in either model., Conclusions: We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research., (Copyright © 2021 by the American Psychosomatic Society.)

Introduction: Electronic cigarettes are now the most commonly used form of tobacco product among youth in the United States. Current evidence suggests that although e-cigarettes are perceived as less harmful and preferred over combustible cigarettes by adolescents, adolescents who try e-cigarettes are at greater risk of transitioning to combustible cigarettes. The genetic and environmental contributions to liability for e-cigarette use have not yet been examined using a behavioral genetic design., Methods: Behavioral genetic models of lifetime and current e-cigarette use and friends who use e-cigarettes were examined among female monozygotic and dizygotic twins., Results: A total of 41 female twin pairs (65.9% monozygotic twins; age = 19.7, SD = 1.6) with complete data on the study variables were included in the present analyses. The majority of the sample (68.1%) had at least some friends who use e-cigarettes. Additive genetic effects on e-cigarette use were not present, but the shared environment explained 98.7% of the variance in lifetime e-cigarette use, 96.6% in current e-cigarette use, and 94.9% in affiliation with friends who use e-cigarettes., Conclusion: This first study on the behavioral genetics of e-cigarette use among adolescents and young adults suggest that environmental factors shared by twins within a family seem to play a predominant role in the initial stages of e-cigarette use, a finding that is consistent with what has been found for tobacco. The findings emphasize the importance of continuing population-based tobacco control interventions to reduce the burden of e-cigarette use among adolescents., Implications: The shared environment significantly influences the initiation and regular use of electronic cigarettes and affiliation with friends who use electronic cigarettes among adolescent and young adult females. These findings underscore the importance of formulating preventive interventions that mitigate the social effects of familial influences on e-cigarette use through social skills training, education on harms of e-cigarettes for young people, or altering social norms regarding initiation of novel tobacco products., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Birthweight discordance is well studied, with less known about longitudinal inter-twin differences in foetal growth., Objective: To examine inter-twin per cent differences in EFW (EFW % ), head (HC % ) and abdominal circumference (AC % ), and femur length (FL % ) across gestation in dichorionic twin gestations and explore associated characteristics., Methods: Foetal biometrics were assessed by ultrasound and EFW calculated at ≤6 study visits among women with dichorionic twin pregnancies enrolled in the NICHD Fetal Growth Studies cohort (US, 2012-2013). Inter-twin per cent difference was defined: ([Size larger twin  - Size smaller twin ]/Size larger twin  × 100). Linear mixed models evaluated per cent differences in foetal biometrics at 15 weeks and their change per week overall and by maternal/neonatal characteristics in unadjusted and adjusted models., Results: In 140 pregnancies, inter-twin per cent differences increased across gestation for EFW (0.18%/week, 95% confidence interval [CI] 0.10, 0.27), HC (0.03%/week, 95% CI 0.00, 0.06), and AC (0.03%/week, 95%CI -0.01, 0.08) but decreased for FL (-0.03%/week, 95% CI -0.09, 0.02). After adjustment, change in EFW % difference across gestation differed by pre-pregnancy body mass index (BMI [kg/m 2 ]; underweight [<18.5]; normal weight [18.5-24.9]; overweight [25.0-29.9]; obese [≥30.0]; P interaction  = .022); and conception method (in vitro fertilisation [IVF], intrauterine insemination, ovulation induction medication, donor egg/embryo, none; P interaction  = .060). While EFW % difference increased with normal pre-pregnancy BMI (0.24%/week, 95% CI 0.12, 0.37), little change was noted with pre-pregnancy obesity (0.01%/week, 95% CI -0.15, 0.17). EFW % difference increased in conceptions without fertility treatments (0.23%/week, 95% CI 0.11, 0.34) but not IVF conceptions (-0.00%/week, 95% CI -0.16, 0.16). Similar patterns of differences across gestation were noted for HC % by conception method (P interaction  = .026) and AC % by pre-pregnancy BMI (P interaction  = .071); changes in HC % differed by parity (nulliparous, multiparous; P interaction  = .004)., Conclusions: EFW % difference increased across gestation in dichorionic twins, but remained stable with pre-pregnancy obesity or IVF conception, patterns mirrored for HC and AC. Research is needed to understand pathologic versus physiologic differential twin growth trajectories., (© 2019 John Wiley & Sons Ltd.)

The incidence of type 1 diabetes (T1D) and some other complex diseases is increasing. The cause has been attributed to an undefined changing environment. We examine the role of the environment (or any changing non-genetic mechanism) in causing the rising incidence, and find much evidence against it: 1) Dizygotic twin T1D concordance is the same as siblings of patients in general; 2) If the environment is responsible for both the discordance among identical twins of patients with T1D and its rising incidence, the twin concordance rate should be rising, but it is not; 3) Migrants from high-to low-incidence countries continue to have high-incidence children; 4) TID incidence among the offspring of two T1D parents is identical to the monozygotic twin rate. On the other hand, genetic association studies of T1D have revealed strong susceptibility in the major histocompatibility complex and many optional additive genes of small effect throughout the human genome increasing T1D risk. We have, from an analysis of previously published family studies, developed a stochastic epigenetic Mendelian oligogenic (SEMO) model consistent with published observations. The model posits a few required recessive causal genes with incomplete penetrance explaining virtually all of the puzzling features of T1D, including its rising incidence and the specific low T1D incidence rates among first-degree relatives of patients. Since historic selection against any causal gene could prevent T1D, we postulate that the rising incidence is because of increasing population mixing of parents from some previously isolated populations that had selected against different causal genes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Evidence that alcohol consumption is inversely associated with long-term coronary artery disease (CAD) mortality independent of genetic and early life environmental factors is lacking., Objective: We evaluated whether alcohol consumption was prospectively associated with CAD mortality risk independent of familial factors., Design: In total, 843 male twins (396 pairs and 51 unpaired twins) aged 42-55 y (mean: 48 y) without baseline CAD reported beer, wine, and spirits consumption at baseline (1969-1973) and were followed up to 2010 in the prospective National Heart, Lung, and Blood Institute Twin Study. Data on usual alcohol consumption over the past year were collected. Outcome was time to event, where the primary event was death from CAD and secondary events were death from cardiovascular disease and all causes. HRs were estimated by using frailty survival models, both overall and within-pair., Results: There were 129 CAD deaths and 219 cardiovascular deaths during 41 y of follow-up. In the whole cohort, after adjustment for caloric intake and cardiovascular disease risk factors, overall HRs per 10-g increment in alcohol intake were 0.94 (95% CI: 0.89, 0.98) for CAD and 0.97 (95% CI: 0.93, 1.00) for cardiovascular mortality. The within-pair adjusted HRs for a twin with 10-g higher daily alcohol consumption than his co-twin were 0.90 (95% CI: 0.84, 0.97) for CAD and 0.95 (95% CI: 0.90, 1.00) for cardiovascular disease mortality in the cohort pooled by zygosity, which remained similar among monozygotic twins. All 3 beverage types tended to be associated with lower CAD mortality risk within-pair to a similar degree. Alcohol consumption was not associated with total mortality risk overall or within-pair., Conclusion: Higher usual alcohol consumption is associated with lower CAD mortality risk, independent of germline and early life environment and adulthood experience shared among twins, supporting a possible causal role of alcohol consumption in lowering CAD death risk. This trial was registered at clinicaltrials.gov as NCT00005124., (© 2015 American Society for Nutrition.)

Microevolutionary projections use empirical estimates of genetic covariation between physical or psychological phenotypes and reproductive success to forecast changes in the population distributions of those phenotypes over time. The validity of these projections depends on relatively consistent heritabilities of fertility-relevant outcomes and consistent genetic covariation between fertility and other physical or psychological phenotypes across generations. However, well-documented, rapidly changing mean trends in the level and timing of fertility may have been accompanied by differences in the genetic mechanisms of fertility. Using a sample of 933 adult twin pairs from the Midlife Development in the United States study, we demonstrate that genetic influences on completed fertility and age at first birth were trivial for the 1920-1935 birth cohort, but rose substantially for the 1936-1955 birth cohort. For the 1956-1970 birth cohort, genetic influences on completed fertility, but not age at first birth, persisted. Because the heritability of fertility is subject to change dynamically with the social context, it is difficult to project selection pressures or the rate at which selection will occur.

Posttraumatic stress disorder (PTSD) is associated with an increased risk of ischemic heart disease, though the pathophysiologic mechanisms remain unclear. Carotid artery intima-media thickness (CIMT) is a measure of subclinical atherosclerosis. We examined whether PTSD and combat exposure were associated with CIMT in Vietnam War-era twins after controlling for shared genetic and childhood factors. Between 2002 and 2010, we studied 465 middle-aged twins from the Vietnam Era Twin Registry who were free from cardiovascular disease. PTSD was diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and CIMT was measured by ultrasound. Mixed-effects regression models were used to examine individual, between-pair, and within-pair associations. Approximately 13% of participants met the criteria for PTSD, and 45% served in the Vietnam Theater. PTSD was associated with 32.7 μm higher CIMT (95% confidence interval (CI): 0.9, 64.5) after adjustment for confounders. The average CIMT for the pair increased by 59.7 μm for each additional twin with PTSD (95% CI: 15.9, 104.2). We found no significant within-pair differences in CIMT when comparing PTSD-discordant co-twins. Results for combat exposure were similar, but its association with CIMT weakened after adjustment for PTSD (95% CI: 7.0, 45.3). Among Vietnam War-era veterans, combat exposure and PTSD are associated with CIMT, though the associations are largely mediated by shared childhood factors., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Prior research suggests a link between academic performance and alcohol use during adolescence, but the degree to which this association reflects actual protective effects continues to be debated. We investigated the role of genetic factors in the association between academic achievement and adolescent alcohol use and whether achievement might constrain the translation of genetic influences on drinking into actual behavior (a Gene × Environment interaction). Analysis of twin data from Add Health (n = 399 monozygotic and dizygotic twin pairs) revealed not only common genetic factors underlying the association between achievement and alcohol consumption but also evidence for a gene-environment interaction. Specifically, the protective effect of achievement operated by moderating heritability of alcohol use, which was particularly salient for adolescents at high genetic risk for alcohol use., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Objectives: The aim of this study was to determine whether post-traumatic stress disorder (PTSD) is associated with coronary heart disease (CHD) using a prospective twin study design and objective measures of CHD., Background: It has long been hypothesized that PTSD increases the risk of CHD, but empirical evidence using objective measures is limited., Methods: We conducted a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Among twin pairs without self-reported CHD at baseline, we selected pairs discordant for a lifetime history of PTSD, pairs discordant for a lifetime history of major depression, and pairs without either condition. All underwent a clinic visit after a median follow-up of 13 years. Outcomes included clinical events (myocardial infarction, other hospitalizations for CHD and coronary revascularization) and quantitative measures of myocardial perfusion by [(13)N] ammonia positron emission tomography, including a stress total severity score and coronary flow reserve., Results: A total of 562 twins (281 pairs) with a mean age of 42.6 years at baseline were included in this study. The incidence of CHD was more than double in twins with PTSD (22.6%) than in those without PTSD (8.9%; p < 0.001). The association remained robust after adjusting for lifestyle factors, other risk factors for CHD, and major depression (odds ratio: 2.2; 95% confidence interval: 1.2 to 4.1). Stress total severity score was significantly higher (+95%, p = 0.001) and coronary flow reserve was lower (-0.21, p = 0.02) in twins with PTSD than in those without PTSD, denoting worse myocardial perfusion. Associations were only mildly attenuated in 117 twin pairs discordant for PTSD., Conclusions: Among Vietnam-era veterans, PTSD is a risk factor for CHD., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The aim of this study is to explore the effect of prenatal androgenization on the clinical eruption of permanent teeth expressing dimorphism and bimaturism. The eruption curves of permanent teeth (except third molars), including those that make up the canine complex (permanent canines, lower first premolars), are compared among opposite sex twins (OS twins) relative to single-born boys and girls. The comparisons are made with regard to three phases of eruption (pierced mucosa, half- erupted, and completely erupted) from a cross-sectional sample of dental casts, using Kaplan-Meier survival and Cox regression analyzes. The casts were collected from 2159 school children from the US Collaborative Perinatal Project, including 39 pairs of OS-twins, of which 12 pairs (30.8%) were Euro-Americans and 27 pairs (69.2%) were of African-American ancestry. The eruption patterns of the incisors, upper first molars, and lower canines were found to be significantly masculinized (delayed) among OS twin girls. The differences in most other teeth were either not significant, or the number of observations of active eruption phases were too few, such as in the upper first molars and incisors, to yield strong evidence and meaningful results. The masculinization of the tooth eruption pattern in OS twin girls is intriguing because of the lower canine responses during puberty, as well as canine primordial formation during early fetal androgenization of their co-twin during the 8th to 14th gestational weeks. The present results offer a challenge for future research exploring tooth eruption mechanisms, and may also highlight some cases of delayed or ectopic canines, which are biased toward females., (Copyright © 2013 Wiley Periodicals, Inc.)

Adolescent dating and sexual activity are consistently associated with risk for depression, yet the pathways underlying this association remain uncertain. Using data on 1,551 sibling pairs (ages 13-18) from the National Longitudinal Study of Adolescent Health, the current study utilized a sibling comparison design to assess whether adolescent dating, sexual intercourse with a romantic partner, and sexual intercourse with a nonromantic partner were associated with higher levels of depressive symptoms independent of familial factors. Results indicated that adolescent dating, in and of itself, was not associated with depressive symptoms. The association between depressive symptoms and sexual activity with a romantic partner was fully accounted for by between-family genetic and shared environmental confounds. In contrast, sexual activity with a nonromantic partner was significantly associated with both mean levels of depressive symptoms and clinically severe depression, even within sibling dyads. This relationship was greater for younger adolescents (<15 years). These results are consistent with a growing body of research demonstrating that relationship contexts may be critical moderators of the psychosocial aspects of adolescent sexual experiences., (2013 APA, all rights reserved)

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

Objectives: We sought to investigate the structure of the genetic and environmental influences on 3 measures of mental well-being., Methods: Analyses focused on the subsample of 349 monozygotic and 321 dizygotic same-sex twin pairs from a nationally representative sample of twins who completed self-report measures of emotional, psychological, and social well-being., Results: The best-fit model contained a common pathway to all 3 measures of well-being, no shared environmental effects, and 1 set of parameters for men and women. Heritability for the latent "mental well-being" factor was high (72%) and best indexed by psychological well-being. Moderate trait-specific genetic effects were seen for emotional and social well-being. Nonshared environmental effects for all measures were mostly trait specific., Conclusions: Genetic influences on the measures of mental well-being reflect a single, highly heritable genetic factor, although some trait-specific genetic influences were seen for emotional and social well-being. Moderate proportions of environmental influences were also shared, but the majority of unique environment was trait-specific.

Background: More years of schooling is generally associated with better health. However, this association may be confounded by unobserved common prior causes such as inherited ability, personality such as patience, or early family circumstances. The twin fixed-effect approach can potentially address this problem by cancelling these factors between twin pairs. The purpose of this study is to identify the causal effects of education on health and health behaviours using a twin fixed-effect approach., Methods: We used twin data from the National Survey of Midlife Development in the United States, 1995-1996. The study population included 302 male [55.6% monozygotic (MZ) and 44.4% dizygotic (DZ)] and 387 female twin pairs (47.3% MZ and 52.7% DZ). A range of health outcomes [perceived global, physical and mental health, body mass index (BMI), waist circumference, waist-hip ratio, number of depressive symptoms] and health behaviours (smoking and physical activity) were examined among twin pairs who were discordant on years of schooling., Results: Among MZ twins, more years of education was associated with better perceived global health. For all other health outcomes/behaviours, the point estimates of the effect of education in the fixed-effect analyses suggested a weak protective association. Among DZ male twins, each additional year of schooling lowered the prevalence of smoking by 32% [odds ratio (OR): 0.68, 95% confidence interval (CI): 0.48-0.97] in the fixed-effect analysis., Conclusion: The widely reported associations between schooling and health outcomes/behaviours may not reflect causal relationships in every instance. Although low statistical power may explain some of the null associations, our twin fixed-effect analyses suggest that at least some cases of the education/health relationship reflect confounding by unobserved third variables.

Objectives: To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis., Design: Cross-sectional study., Setting: Internet-based autism registry for US residents., Participants: Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin., Main Exposures: Zygosity and sex., Outcome Measures: Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening., Results: Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases., Conclusions: Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid.

Background: A growing number of studies have suggested a link between social capital and health. However, the association may reflect confounding by factors, such as personality or early childhood environment, that are unmeasured prior common causes of both social capital and health outcomes. The purpose of this study was to investigate the impact of social capital on physical and mental health among adult twins in the U.S., Methods: A cross-sectional national survey of twins within the National Survey of Midlife Development in the U.S. (MIDUS), 1995--1996 was analyzed in 2007. The study population included 944 twin pairs (37.2% monozygotic [MZ] and 62.8% dizygotic [DZ]). Data were obtained on individual-level social capital variables (social trust, sense of belonging, volunteer activity, and community participation); health outcomes (perceived physical and mental health, depressive symptoms and major depression); and individual covariates (age, gender, race, education, working status, and marital status). A fixed-effects model was used to examine health status among twin pairs who were discordant on levels of social capital., Results: In the individual data analysis, social trust, sense of belonging, and community participation were each significantly associated with health outcomes. In the fixed-effects model, physical health remained significantly positively associated with social trust among MZ and DZ twins. However, major depression was not associated with social capital., Conclusions: The present study is the first to find the independent positive effect of social trust on self-rated physical health using fixed-effects models of twin data. The results suggest that the association between social capital and physical health status is not explained by unobserved confounds, such as personality or early childhood environment.

This study examined the nature of the relationship among lifetime major depression, smoking, and nicotine dependence. Subjects were 8,169 male twins from the Vietnam Era Twin Registry. Biometrical modeling demonstrated a genetic influence on daily smoking, nicotine dependence, and major depression, and a family environmental influence on daily smoking. Genetic factors influencing nicotine dependence also strongly influenced major depression. We also compared probands with a history of major depression (n = 398) from pairs discordant for major depression, their nondepressed cotwins (n = 364), and controls (n = 1,863) on a number of secondary smoking outcomes. Major depression was associated with current daily smoking and certain nicotine withdrawal symptoms. Individuals with a familial vulnerability for major depression, even without a personal history of major depression, were more likely to smoke despite a serious illness and to report nervousness, restlessness, difficulty concentrating, and depressed mood during past quit attempts. Among the 237 monozygotic pairs discordant for major depression, depressed probands were more likely to have a lifetime history of nicotine dependence than were cotwins. Findings extend Kendler and colleague's (1993) study of female twins by demonstrating in men that shared genetic factors predispose not only to major depression and daily smoking but also to major depression and nicotine dependence.

Rationale: Studies have suggested heightened anxiety among adults with asthma; the mechanism of this association is not known., Objectives: To determine the association between post-traumatic stress disorder (PTSD) symptoms and asthma among adults, and to examine if this association is due to confounding by environmental and genetic factors., Methods: Data were obtained from twins in the Vietnam Era Twin Registry, which includes male veteran twin pairs born between 1939 and 1956 who served during the Vietnam era (1965-1975). Measurements included a symptom scale for PTSD, history of a doctor diagnosis of asthma, and sociodemographic and health confounding factors. Co-twin control analytic methods used mixed-effects logistic regression to account for the paired structure of the twin data and to examine the association between PTSD symptoms and asthma in all twins. Separate analyses were conducted within twin pairs and according to zygosity., Measurements and Main Results: PTSD symptoms were associated with a significantly increased likelihood of asthma (P(trend) < 0.001) even after adjustment for confounding factors. Among all twins, those in the highest quartile of PTSD symptoms were 2.3 times as likely (95% confidence interval, 1.4-3.7) to have asthma compared with those in the lowest quartile. These findings persist when examined within twin pairs and when stratified by zygosity., Conclusions: Symptoms of PTSD were associated with an elevated prevalence of asthma. Even after careful adjustment for familial/genetic factors and other potential confounding factors, an association between PTSD symptoms and asthma remains. Efforts to understand this comorbidity may be useful in identifying modifiable environmental risk factors contributing to this pattern and therefore in developing more effective prevention and intervention strategies.

Background: Little is known about the interplay of genotypes and malleable risk factors in influencing adolescent psychiatric symptoms and disorders. Information on these processes is crucial in designing programs for the prevention of psychiatric disorders., Objective: To assess whether latent genetic factors and measured parent-child relationships interact (G x E) in predicting adolescent antisocial behavior and depression., Design: We characterized risk of antisocial behavior and depression in adolescents by means of a genetically informed design. We used in-home questionnaire and observational measures of adolescent outcomes and environmental moderators (parenting), and a latent variable behavior genetic analytic model., Setting: A nationally distributed sample recruited from random-digit dialing and national market panels., Participants: A total of 720 families with at least 2 children, 9 through 18 years old, stratified by genetic relatedness (monozygotic and dizygotic twins, full biological siblings in nondivorced and stepfamilies, and half-siblings and biologically unrelated siblings in stepfamilies)., Main Outcome Measures: Antisocial behavior and depressive symptoms., Results: There was an interaction of genotype and both parental negativity and low warmth predicting overall antisocial behavior, as well as aggressive and nonaggressive forms of antisocial behavior, but not depression. Genetic influence was greater for adolescent antisocial behavior when parenting was more negative or less warm. Genotype-environment correlation was partialled out in the analysis and thus did not account for the results., Conclusion: This study demonstrates, on the basis of careful measurement and appropriate analytic methods, that a continuous measure of parenting in the normative range moderates the influence of genotype on antisocial behavior.

The Vietnam Era Twin Study of Aging (VETSA) is a large-scale investigation of cognitive aging from middle to later age. The intended sample of 1440 twin subjects is recruited from the Vietnam Era Twin Registry (VETR), a registry of middle-aged male-male twin pairs who both served in the military during the Vietnam conflict (1965-1975). VETSA employs a multitrait multimethod approach to cognitive assessment to focus on the genetic and environmental contributions to cognitive processes over time, as well as the relative contributions to cognitive aging from health, social, personality, and other contextual factors. The cognitive domains of episodic memory, working memory, abstract reasoning, and inhibitory executive functioning are assessed through neuropsychological testing. In addition, VETSA obtains the participant's score on the Armed Forces Qualification Test, taken at the time of induction into the military around age 20 years, and re-administers the test. Two other projects--VETSA Cortisol and VETSA Magnetic Resonance Imaging--are also in progress using subsamples of the VETSA twins. Prior waves of data collection by VETSA investigators using the VETR have provided historical data on physical and mental health, while future waves of VETSA data collection are planned every 5 years. These methods will provide data on multiple phenotypes in the same individuals with regard to genetic and environmental contributions to cognitive functioning over time, personality and interpersonal risk and protective factors, stress and cortisol regulation, and structural brain correlates of aging processes.

The Duke Twins Study of Memory in Aging is an ongoing, longitudinal study of cognitive change and dementia in the population-based National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry of World War II Male Veterans. The primary goal of this study has been to estimate the overall genetic and environmental contributions to dementia with a specific focus on Alzheimer's disease. An additional goal has been to examine specific genetic and environmental antecedents of cognitive decline and dementia. Since 1989, we have completed 4 waves of data collection. Each wave included a 2-phase telephone cognitive screening protocol, followed by an in-home standardized clinical assessment for those with suspected dementia. For many participants, we have obtained postmortem neuropathological confirmation of the diagnosis of dementia. In addition to data on cognition, we have also collected information on occupational history, medical history, medications and other lifetime experiences that may influence cognitive function in late life. We provide an overview of the study's methodology and describe the focus of recent research.

This article describes the design and data availability for samples of genetic pairs in the National Longitudinal Study of Adolescent Health (Add Health). Add Health provides unique samples of genetic pairs that are nationally representative and followed longitudinally from early adolescence into young adulthood with 3 in-home interviews and a 4th interview planned for 2007 to 2008. The design of Add Health included an embedded genetic sample of more than 3000 pairs of individuals with varying genetic resemblance, including monozygotic twins, dizygotic twins, full siblings, half siblings, and unrelated siblings who were raised in the same household. Add Health has collected rich longitudinal social, behavioral, and environmental survey data, as well as buccal cell DNA from a subsample of the genetic sample (N = 2612). Add Health has an enlightened dissemination policy and to date has released phenotype and genotype data to more than 3000 researchers in the scientific community.

This paper examines genetic contribution to suicidal behaviors and other risk factors associated with suicidal behavior among adolescents in the U.S. Using adolescent twin data in the National Longitudinal Study of Adolescent Health (N = 1448), we compared concordance in suicidal ideation and attempt among monozygotic (MZ) and dizygotic (DZ) twins. Heritability of risk factors for suicidal behaviors also was examined using Pearson correlation and mixed-model analyses. A trend of higher concordance in suicidal ideation and attempt was found among MZ than DZ twins but the difference was not statistically significant by the stringent test of bootstrapping analysis. Evidence of heritability was found for several suicide risk factors. The percentage of variance explained by heritability was larger among female twins for depression, aggression, and quantity of cigarettes smoked in comparison to heritability estimates for male twins. However, estimated heritability was larger among male than female twins for alcohol use and binge drinking. Heritability influence was negligible among both sexes for other drug use. Risk factors for suicidal behaviors among adolescents may be heritable. Gender differences found in the heritability of some suicide risk factors suggest these genetic contributions are gender specific. Future research examining potential interactions between expression of genetic influence and particular environmental contexts may enhance prevention and intervention efforts.

Objective: To address the inconsistency in the reported concordance of multiple sclerosis (MS) among twins by zygosity, sex, and latitude., Methods: Four hundred eighteen medically documented monozygotic (MZ) and 380 same-sex dizygotic (DZ) pairs were ascertained from 1980 to 1992 and followed. The study population was representative of twins with multiple sclerosis. Twins from Canada and adjacent US states (at or above 41-42 degrees N) were considered "northern," and ancestry was dichotomized from descent from high-risk populations. Diagnosis before median age 29.3 years was considered "early.", Results: The MZ/DZ concordance ratio was 2.9 (95% confidence interval [CI], 1.0-8.9) among men and 2.6 (95% CI, 1.5-4.5) among women. The average age at northern diagnosis was independent of ancestry and 2 years earlier for both MZ (p < 0.02) and DZ (p < 0.01) patients. Among DZ twins, concordance was independent of all characteristics. Among MZ twins, concordance was 1.9 times (95% CI, 1.2-3.2) greater among northern twins, 1.9 (95% CI, 1.1-3.6) times greater among twins with high-risk ancestry, and 2.1 (95% CI, 1.2-3.6) times greater if diagnosis was early. Ancestry and early diagnosis made independent significant contributions to the differential concordance by latitude., Interpretation: Multiple sclerosis is similarly heritable by sex, and the apparent variation in MZ concordance by latitude is influenced by environmental and genetic factors.

Twin studies of lipids have almost exclusively involved Caucasians. People of African descent are known to show a healthier lipid profile, but relatively little is known about ethnic differences in genetic and environmental influences on lipids. One hundred and six African American (AA) and 106 European American (EA) twins (30 singletons and 91 complete pairs: 49 monozygotic, 21 dizygotic and 21 opposite-sex) from the south-eastern United States were studied (mean age 17.9 +/- 3.2 years; 79% fasting). Lipids were assayed with the Cholestech LDX system. Analyses were adjusted for fasting status. Generalized estimating equations were used to test for the effects of sex and ethnicity on means, controlling for the dependence within twin pairs. Structural equation modeling was used to estimate genetic and environmental effects on each lipid variable. Females showed higher high-density lipoprotein (HDL) values than males (p < .001) and AAs showed higher HDL values than EAs (p < .001). EA males had higher triglyceride values than other groups (p = .02). All parameter estimates could be set equal across sex. Parameter estimates for total cholesterol, triglycerides and HDL could be set equal across ethnicity. The best fitting model for low-density lipoprotein (LDL) showed higher heritability in AAs (.92) than EAs (.69). Heritabilities ranged from 69% to 92%, with remaining variation explained by nonshared environmental effects. Adjustment for body mass index had virtually no effect on the heritability estimates. In this first twin study on lipids to include AAs, no ethnic differences in heritability were found except for LDL, where AAs exhibited higher estimates.

Context: Although pathological gambling (PG) and major depression (MD) frequently co-occur, little is known regarding the relative contributions of environmental and genetic factors to the codevelopment of the disorders., Objectives: To estimate environmental and genetic contributions to PG and MD as defined in DSM-III-R and the lifetime co-occurrence of PG and MD., Design: Survey data from the Vietnam Era Twin Registry were examined in biometric models., Setting: Telephone interview., Participants: Of 10, 253 eligible participants, 7869 were successfully interviewed., Main Outcome Measures: Estimated genetic, shared environmental, and unique environmental contributions to PG and MD and their lifetime co-occurrence in bivariate models., Results: Elevated odds ratios for MD were associated with those of PG (4.06; 95% confidence interval, 2.68-6.13), and the association remained significant following adjustment for sociodemographic and other psychiatric variables (odds ratio = 1.98; 95% confidence interval, 1.14-3.45). The best-fitting bivariate model indicated that 66% of the variance in PG and 41% of the variance in MD were owing to genetic factors, and 34% of the variance in PG and 59% of the variance in MD were owing to unique environmental factors. There was a substantial correlation between the genetic components of PG and MD (r(A) = 0.58), with 34% of the genetic variance for each disorder also contributing to that of the other. The best-fitting model estimated that 100% of the total overlap between PG and MD was genetic., Conclusions: The correlation between PG and MD in middle-aged men appears to be largely influenced by overlapping genetic factors. Future research is needed to determine the extent to which these findings extend to other groups (eg, women), identify specific genes, and generate improved prevention and treatment strategies.

Objective: To estimate the genetic and environmental contributions to oppositional defiant behavior (ODB) from mother, father, and teacher report using the Conners Revised Short Forms in a large twin sample., Method: ODB data were collected from 1,595 mothers, 1,114 fathers, and 793 teachers of 7-year-old twin pairs from the Netherlands Twin Registry in the 1990-1992 cohort with an 80% response rate. Models were fit for each informant to determine the genetic, environmental, gender, and informant influences on ODB., Results: Genetic analyses of the ODB quantitative scale showed additive genetic (A) by mother (55%), by father (57%), and by teacher (21% girls, 38% boys) unique environmental (E) (mother, 22%; father, 29%; teacher, 48% girls, 39% boys) and shared environmental (C) (mother, 14%; father, 23%; teacher, 31% girls, 23% boys) influences., Conclusions: Additive genetic and unique environmental factors account for the majority of the influences on ODB for boys and girls by all informants.

Background: Important controversies exist about the extent to which people's health status as adults is shaped by their living conditions in early life compared to adulthood. These debates have important policy implications, and one obstacle to resolving them is the relative lack of sufficient high-quality data on childhood and adult socioeconomic position and adult health status. We accordingly compared the health status among monozygotic and dizygotic women twin pairs who lived together through childhood (until at least age 14) and subsequently were discordant or concordant on adult socioeconomic position. This comparison permitted us to ascertain the additional impact of adult experiences on adult health in a population matched on early life experiences., Methods and Findings: Our study employed data from a cross-sectional survey and physical examinations of twins in a population-based twin registry, the Kaiser Permanente Women Twins Study Examination II, conducted in 1989 to 1990 in Oakland, California, United States. The study population was composed of 308 women twin pairs (58% monozygotic, 42% dizygotic); data were obtained on childhood and adult socioeconomic position and on blood pressure, cholesterol, post-load glucose, body mass index, waist-to-hip ratio, physical activity, and self-rated health. Health outcomes among adult women twin pairs who lived together through childhood varied by their subsequent adult occupational class. Cardiovascular factors overall differed more among monozygotic twin pairs that were discordant compared to concordant on occupational class. Moreover, among the monozygotic twins discordant on adult occupational class, the working class twin fared worse and, compared to her professional twin, on average had significantly higher systolic blood pressure (mean matched difference = 4.54 mm Hg; 95% confidence interval [CI], 0.10-8.97), diastolic blood pressure (mean matched difference = 3.80 mm Hg; 95% CI, 0.44-7.17), and low-density lipoprotein cholesterol (mean matched difference = 7.82 mg/dl; 95% CI, 1.07-14.57). By contrast, no such differences were evident for analyses based on educational attainment, which does not capture post-education socioeconomic position., Conclusion: These results provide novel evidence that lifetime socioeconomic position influences adult health and highlight the utility of studying social plus biological aspects of twinship.

Context: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood., Objective: To investigate the impact of genetic and environmental factors., Participants: Living twins in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927., Methods: Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components., Main Outcome Measure: Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs., Results: Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected., Conclusions: Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness.

Cannabis and other illicit drugs are often used or abused comorbidly. Two competing theories to explain this comorbidity are (i) the phenotypic causation (gateway) model and (ii) the correlated liabilities model. We used data from 1191 male and 934 female same-sex twin pairs to test 13 genetically informative models of comorbidity. Models were fit separately for use and abuse/dependence in both sexes. The correlated liabilities model provided a good fit to the data for cannabis and other illicit drug use, as well as abuse/dependence. The relationship between the use or abuse of cannabis and other illicit drugs is not entirely phenotypic, as depicted by the random multiformity of cannabis model, which is an adaptation of the gateway model. The comorbidity appears to arise from correlated genetic and environmental influences. There is some evidence for a model in which high-risk cannabis users may be at increased risk for other illicit drug use. For abuse/dependence, a model with causal pathways between the liability for cannabis and other illicit drug abuse/dependence also fits well. Overall, our results suggest that the use and abuse/dependence of cannabis and other illicit drugs are strongly linked via common risk factors that jointly influence their individual liabilities.

Objective: To examine the effect of length variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on individual differences in cardiovascular response to psychological challenge., Methods: Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) responses to computerized versions of two psychological challenges, the Stroop Color-Word Interference Test and mental arithmetic, were measured among 131 monozygotic (MZ) and 60 dizygotic (DZ) male or female (same-sex) European-American twin pairs. Among the 382 participants, 140 were homozygous for the "long" allele (l/l) at 5-HTTLPR, 61 were homozygous for the "short" allele (s/s), and 181 participants had one long and one short allele (l/s). Association and sib-pair analyses were performed to characterize genetic associations., Results: In the full sample, 5-HTTLPR was associated with HR reactivity to psychological challenge, albeit in interaction with sex. Task-elicited HR responses of women homozygous for the short allele were significantly greater than among: a) men of the same genotype; and b) women having either one (l/s) or two (l/l) long alleles at 5-HTTLPR. SBP and DBP responsivity was unrelated to genotype. These results were corroborated on reanalysis in two genetically independent subsamples. Variability at 5-HTTLPR also predicted HR reactivity in sib-pair analyses among DZ twins., Conclusions: These results suggest that the commonly observed sex difference in HR reactivity may be, in part, genetically mediated and perhaps occur only among individuals homozygous for the short allele at 5-HTTLPR.

The etiology of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function. Recent genome-wide searches reported several susceptibility loci for Crohn's disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn's disease will have a major impact on the understanding of the genetics of this disease.

The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI< or =0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity. A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g., physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics, and early shared environment.

We estimate the magnitude of genetic and shared environmental contributions to risk of initiation and maintenance of smoking. Genetic models were fitted to data from 2,204 male-male monozygotic and 1,793 male-male dizygotic twin pairs from the Vietnam Era Twin Registry who responded to smoking questions on a 1987 mail and telephone survey. The best fitting model allowed for both genetic and shared environmental effects on smoking initiation, accounting for 50% and 30% of the variance in risk, but allowed for only genetic effects, (accounting for 70% of the variance in risk), on persistence in smoking among those who had become regular smokers. This finding of a major genetic influence on smoking persistence confirms similar results from studies in Scandinavia and Australia. The role of heritable traits such as nicotine sensitivity should be addressed in smoking prevention and cessation efforts.

Given the current explosion of knowledge of the genetics and molecular biology of cancer, the possibility of widespread testing for inherited predisposition to cancer has been raised. The main objective of this study was to assess the effect of inherited predisposition on cancer mortality among the National Academy of Sciences-National Research Council Twin Registry. The twins were white male United States veterans of World War II, who were born during the period 1917-1927. The follow-up period was from 1946 to 1990, and some cause of death was determined with the use of death certificates. We compared concordance for death from cancer among 5690 monozygotic twin pairs to that among 7248 dizygotic pairs. A possible effect of inherited predisposition to death from cancer was considered present if concordance for cancer mortality among monozygotic twin pairs was greater than it was among dizygotic twin pairs. Among monozygotic and dizygotic twins, a total of 1918 cancer deaths was observed. Concordance for death from cancer at all sites among monozygotic twins was higher than it was among dizygotic twins (overall rate ratio, 1.4; 95% confidence interval, 1.0-2.0). For each zygosity group, two or fewer pairs were observed to be concordant for death from cancer of a specific site, with the exception of lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of this study was to assess the childhood growth of twin children in terms of the effects of intrauterine growth retardation (IUGR) and discordancy at birth on the incidence and severity of stunting and discordancy in current height and weight. The study was part of a cross-sectional field project conducted at the Annual Twins Days Festival in Twinsburg. Ohio, USA, during 1990, 1991, and 1993, and including all twin children between 2 and 12 years of age. Mothers of twins were interviewed regarding their children's birthweights and gestational age; the twin children were measured for their current heights and weights. The study population included 990 twin children, including 555 boys and 435 girls, of which there were 254 boy pairs and 194 girls pairs. Birthweight for gestational age and current weight and height were each converted into Z-scores and characterized as severe (Z-score < -2,0), or moderate IUGR or stunting (Z-score > -2.0 and < -1.2). For the present study discordancy in birthweight, and current height and weight was calculated for like-gender twin pairs. Only twin children with severe IUGR at birth showed an increased risk of stunting in their current height or weight, and this risk was only for moderate, not severe, stunting. Boy twins with severe IUGR at birth were at increased risk of moderate stunting in their current weight (OR 2.67, 95% CI 1.55, 4.58, p = 0.002), while girl twins with severe IUGR at birth were at increased risk of moderate stunting in their current height (OR 4.09, 95% CI 1.49, 10.99, p = 0.003). Among like-gender twin pairs, there were no differences in mean or categories of birthweight or current weight discordancy, but boy twin pairs did show a significantly greater proportion of current weight discordancy compared to girl twin pairs (p = 0.005). Overall, there was a significant tendency for differences in height and weight between like-gender twin pairs to disappear over time, with the effect being greater for boy twin pairs. We conclude from these findings that twin children tend to overcome growth retardation and discordancy present at birth, and although children who had severe IUGR or discordancy at birth were more likely to have some residual moderate stunting or discordancy in height or weight, they still tended to be within normal values for their gender and current age.

Prior studies have suggested that the risk of testicular cancer among dizygotic twins may exceed that among monozygotic twins or the general population. Cryptorchidism is associated with testicular cancer and twinship, and therefore might potentially explain the findings of the prior studies. In 1993-1994, when they were 66 to 77 years of age, 14,326 twin individuals in the National Academy of Sciences-National Research Council Twin Registry were interviewed by telephone. A history of testicular cancer was reported by 5 (0.08%) of 5951 monozygotic twins and 11 (0.16%) of 6992 dizygotic twins. Follow-up interviews concerning testicular cancer risk factors and treatment were able to be administered to 4 of the monozygotic and 9 of the dizygotic twins reporting testicular cancer. A history of cryptorchidism was reported in the follow-up interview by only one dizygotic twin. Our data agree with the results of prior studies reporting a more frequent occurrence of testicular cancer among dizygotic than monozygotic twins. Although somewhat limited by small numbers, our study also suggests that the findings of increased testicular cancer in dizygotic twins are not explained simply by increased occurrence of cryptorchidism in twins.

We investigated the mediating role of genetic factors in the clustering of hypertension, diabetes, and obesity, using the twin registry maintained by the National Academy of Sciences--National Research Council. The study sample included 2,508 male twin pairs born between 1917 and 1927 who responded to a mailed questionnaire that covered demographic variables, cardiovascular risk factors, and health behaviors. The incidence of hypertension and diabetes in this cohort was ascertained from subjects' self-report of a physician diagnosis and/or the use of prescription medications. The body-mass index calculated from self-reports of height and weight was used as a measure of obesity. Descriptive analyses indicated probandwise concordance rates of 34.0%, 31.2%, and 32.7%, respectively, for the joint occurrences of hypertension and diabetes, hypertension and obesity, and diabetes and obesity in MZ twin pairs. Corresponding concordance rates in DZ twin pairs were 8.1%, 14.9%, and 2.8%. The probandwise concordance for the clustering of all three conditions in the same individuals was 31.6% in MZ pairs and 6.3% in DZ pairs (relative risk 5.0; X2(1) = 2.6; P < .15). Multivariate genetic modeling of the correlation in liabilities to develop these conditions suggested the presence of a common latent factor mediating the clustering of hypertension, diabetes, and obesity in this twin sample. This common factor was influenced by both genetic and environmental effects (59% 8 genetic, 41% environmental). The genetic influences on the common latent factor were due to dominant rather than additive sources; the environmental influences appeared to be specific rather than shared by co-twins.

Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15,924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur.

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

We interviewed families of 71 patients registered in the National Wilms Tumor Study and identified as having a twin sibling. Questions concerning zygosity and the occurrence of congenital anomalies and other forms of cancer in the twins were asked. Of the 71 twin pairs, 35 were dizygotic, 31 were monozygotic, and 5 were of unknown zygosity. The only pair concordant for Wilms tumor was dizygotic, leading to a heritability estimate of zero. In a monozygotic pair, one twin was diagnosed with Wilms tumor and the other with medulloblastoma. The estimated relative risk of Wilms tumor and childhood cancer in the co-twin was 250 times and 10 times the population rate, respectively. Four discordant pairs had a family history of Wilms tumor, suggesting that the penetrance of the condition is not complete. Because of the small sample size, caution should be exercised in the interpretation of these results.

Data from 4,029 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975) were used to examine genetic and non-genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self-reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self-reported combat experiences.

It is estimated that at least one dizygotic (DZ) twin maternity in twelve is preceded by superfecundation (the fertilization of two ova by sperm from different coitions). Presumably this parameter varies from population to population eg. with coital rates and rates of double ovulation. Sometimes superfecundation occurs by two different men. The frequency with which this occurs must depend on rates of infidelity (promiscuity). It is suggested that among DZ twins born to married white women in the U.S., about one pair in 400 is bipaternal. The incidence may be substantially higher in small selected groups of dizygotic twin maternities, eg. those of women engaged in prostitution.

The National Heart, Lung and Blood Institute (NHLBI) twin study is a collaborative, longitudinal study of the role of genetic risk factors on subsequent cardiovascular disease processes in 514 pairs of white, male World War II and Korean veteran twins born between 1917 and 1927. This paper describes the sampling procedures and zygosity determination at the initial examination, participation by the cohort members at later examinations, and a summary of the variables provided for Genetic Analysis Workshop 8 (GAW8).

Background: The results of twin and family studies suggest that heredity has a small influence on smoking behavior., Methods: We conducted a genetic analysis of several aspects of smoking behavior among subjects in the National Academy of Sciences-National Research Council Twin Registry. The registry includes male twins who were born in the United States between 1917 and 1927 and who were members of the armed services during World War II. Information on smoking history was available for 4775 pairs of twins, who were first surveyed in 1967 through 1969, when they were 40 to 50 years old, and then re-surveyed in 1983 through 1985, when they were 56 to 66. Eighty percent of the subjects in this cohort had smoked at some time in their lives, 60 percent were smokers in 1967 through 1969, and 39 percent were smoking in 1983 through 1985. Similarities between twins in smoking habits at base line and at the second follow-up 16 years later were examined. The comparison of concordance for smoking between monozygotic and dizygotic twins was used to assess the relative contribution of familial and genetic factors., Results: In 1967-1969 survey the ratio of observed to expected concordance for smoking was higher among the monozygotic twins than among the dizygotic twins for those who had never smoked (overall rate ratio, 1.38; 95 percent confidence interval, 1.25 to 1.54), for former smokers (overall rate ratio, 1.59; 95 percent confidence interval, 1.35 to 1.85), for current cigarette smokers (overall rate ratio, 1.18; 95 percent confidence interval, 1.11 to 1.26), and for current cigar or pipe smokers (overall rate ratio, 1.60; 95 percent confidence interval, 1.22 to 2.06). The data also suggest genetic influences on quitting smoking. Monozygotic twins were more likely than dizygotic twins to be concordant for quitting smoking (overall rate ratio, 1.24; 95 percent confidence interval, 1.06 to 1.45)., Conclusions: In this cohort of adult male twins, there were moderate genetic influences on lifetime smoking practices.

The UCLA Registry for Genetic Studies in Autism was established in 1980 to test the hypothesis that genetic factors may be etiologically significant in subsets of patients. To date 61 pairs of twins have enrolled and 40 meet research diagnostic criteria for autism. The authors found a concordance for autism in these 40 pairs of 95.7% in the monozygotic twins (22 of 23) and 23.5% in the dizygotic twins (four of 17).