Male Twin Pairs Research Articles

Forms of cannabis and cocaine: a twin study.

Cannabis and cocaine are illicit psychoactive substances that have fallen under intense scrutiny by epidemiologists and behavioral geneticists. However, most analyses have used a composite variable to represent the use of these two drugs. For example, the composite variable of cannabis use often includes use of marijuana or hashish. Similarly, cocaine use involves different preparations (crack vs. cocaine hydrochloride) and varying routes of administration (intranasal insufflation vs. smoking). While there is some epidemiological evidence for the difference in addictive potentials between crack and intranasal cocaine, genetically informative studies have not examined the relationship between the forms of cannabis or cocaine. We used data from male and female same-sex twin pairs to examine the extent of genetic, shared environmental, and unique environmental overlap between (i) marijuana and hashish for cannabis use and (ii) intranasal and crack cocaine for cocaine use. Bivariate Cholesky models were fit using the structural equation modeling software Mx. Our results indicate that for both drugs, the individual drug forms show a complete overlap of genetic factors and a substantial overlap of shared environmental influences. While marijuana and hashish share a moderate proportion of their unique environment, crack and intranasal cocaine only show a modest overlap of unique environmental factors, adding some evidence for form-specific environmental factors. In conclusion, there is substantial overlap of familial factors between forms of a single drug and preference is primarily determined by unique environmental influences. These findings also reinforce the validity of composite variables in epidemiological and genetic research.

Physical activity and genetic influences in risk factors and aging: a study on twins.

The association between physical activity and a decreased risk of age-correlated diseases appears to be well established. Nevertheless, the relation between past life style and current health in the elderly is likely to be affected by interactions of environmental and genetic factors in mediating the effects of exercise on disease prevention. As a contribution to this general issue, a retrospective twin study was undertaken so as to take advantage of the classical twin method in assessing genetic influences on health status in the elderly. A more specific aim was to possibly identify and compare genetically identical elderly twins with substantial differences in previous exposure to physical activity, but otherwise similar life style factors and events, thereby allowing the application of the co-twin case-control method, a powerful experimental approach in which even a few cases may prove significant. The study involved the assessment of general health status (based on structured interviews, clinical examination and several functional and laboratory analyses) and life style in 27 male twin pairs, aged 71.0 +/- 2.6 and classified (through DNA analysis) as 13 monozygotic and 14 dizygotic pairs. Past and present physical activity were evaluated through the Modified Baecke Questionnaire for Older Adults. In general, higher intrapair correlations in monozygotic than dizygotic pairs for almost all clinical variables were found, thereby confirming the relevance of genetic effects. More specifically, five monozygotic pairs discordant for past physical activity were found: contrary to expectations and, notwithstanding this major difference, they did not appear to be less similar than other pairs with respect to general health status. More data are clearly needed, and the implications of these findings, if confirmed, may leave room for complex interpretations. Tentatively, however, one might be led to conclude that whatever protective role physical activity and other life style variables clearly play in general health, this may in the end be unable to offset strong genetic dispositions, particularly so when it comes to major risk factors, which, after all, is perhaps only reasonable.

Genetic influence on prolonged gestation: A population-based Danish twin study

ObjectiveThe purpose of this study was to test a possible genetic component to prolonged gestation. Study designThe gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the Danish Medical Birth Register. A total of 2588 same-sex twin pairs of whom both cotwins became parents during 1978 to 1996 were identified. ResultsThe concordance rate for female twin pairs for a gestation of ≥41 weeks and ≥42 weeks was higher for monozygotic twin pairs than for dizygotic twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic factors. ConclusionMaternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found.

Role of candidate genes in the responses to long-term overfeeding: review of findings.

An overfeeding experiment conducted with 12 pairs of young male identical twins revealed that genetic factors were likely to play an important role in the response to caloric affluence. Significant intrapair resemblance was observed for the overfeeding-induced changes in body weight, fat mass, abdominal fat, fasting insulin, fasting cholesterol and triglycerides. In an attempt to define the molecular basis of these genotype-energy balance interaction effects, a panel of candidate genes has been investigated. Among the most significant findings, an adipsin polymorphism was associated with increases in body weight, total fat mass and subcutaneous fat in response to overfeeding. In addition, the beta2 adrenergic receptor gene Gln27Glu polymorphism showed a strong association with the gains in body weight and subcutaneous fat. Only a few markers were related to abdominal fat changes and, among them, the adipsin Hinc II polymorphism was associated with both computed tomography (CT)-measured abdominal visceral and total fat. The changes in insulin parameters brought about by long-term overfeeding were influenced most consistently by leptin receptor (LEPR) Gln223Arg and insulin-like growth factor-II Apa I polymorphisms. The LEPR Gln223Arg variant was also associated with the changes in plasma total triglycerides and high-density lipoprotein cholesterol concentrations. Further research with larger sample sizes should make it possible to identify the specific contributions of DNA sequence variations at multiple candidate gene loci in the complex response to chronic positive energy balance.

Effects of long-term negative energy balance with exercise on plasma lipid and lipoprotein levels in identical twins

Plasma lipid and lipoprotein concentrations were measured before and after a 58,000 kcal (244 MJ) negative energy balance protocol induced entirely by supervised endurance exercise over a 93-day period in seven pairs of young sedentary and healthy male monozygotic twins. The negative energy balance induced significant changes in all measures of body weight and composition except fat free mass. The mean weight loss was 5.0±0.6 kg, and it was entirely accounted for by the loss of body fat. In response to the program, improvement in the plasma lipid profile was seen including decreases in plasma total ( P=0.028) and low density lipoprotein (LDL) ( P=0.004) cholesterol; total cholesterol/high density lipoprotein (HDL) cholesterol ratio ( P=0.002); and HDL apolipoprotein A–I concentration ( P=0.062). Statistically significant within-pair resemblance was found for the changes in total and very low density lipoprotein (VLDL) cholesterol; total, VLDL and LDL triglycerides, and total, VLDL and LDL apolipoprotein B. The findings suggest that favorable changes in the lipid profile can be obtained through chronic negative energy balance achieved by clamping daily energy intake and adding daily moderate intensity exercise even in persons with relatively normal lipid levels at baseline. Furthermore, within-pair resemblance among twin brothers strongly suggests that genetic differences partially account for the variation in the response of lipids and lipoproteins to the negative energy balance protocol.

Agoraphobic behavior and panic attack: a study of male twins

We used data from 3372 pairs of male twins from the Vietnam Era Twin Registry to examine comorbidity and familial influences on the frequently observed association between agoraphobic behavior and panic. Due to low prevalence of DSM-III-R-defined panic disorder, we also examined subjects who had experienced at least one panic attack during their lives. Agoraphobic behavior among individuals with a history of panic attacks showed familial aggregation (odds ratio=5.7; P=.018). Probands with panic attacks and agoraphobic behavior and their co-twins had higher risk of major depression than probands without agoraphobic avoidance and their co-twins ( P=.01). Groups did not differ for alcohol dependence or antisocial personality. Agoraphobic behavior associated with panic attack is familial and associated with comorbid major depression. Agoraphobia following panic attack does not seem to reflect severity as agoraphobic behavior in the proband was unrelated to risk of panic attacks in the co-twin.

Twin study of genetic and environmental influences on adult body size, shape, and composition.

To investigate the genetic and environmental influences on adult body size, shape, and composition in women and men, and to assess the impact of age. In this cross-sectional study of 325 female and 299 male like-sex healthy twin pairs, on average 38 y old (18-67 y), we determined zygosity by DNA similarity, and performed anthropometry and bioelectrical impedance analysis of body composition. The contribution to the total phenotypic variance of genetic, common environment, and individual environment was estimated in multivariate analysis using the FISHER program. Further, these variance components were analysed as linear functions of age. In both women and men genetic contributions were significant for all phenotypes. Heritability for body mass index was 0.58 and 0.63; for body fat%, 0.59 and 0.63; for total skinfolds, 0.61 and 0.65; for extremity skinfolds 0.65 and 0.62; for truncal skinfolds, 0.50 and 0.69; for suprailiac skinfolds, 0.49 and 0.48; for waist circumference, 0.48 and 0.61; for hip, 0.52 and 0.58; for lean body mass/height2, 0.61 and 0.56; and for height, 0.81 and 0.69, respectively. There was no strong evidence of common environmental effects under the assumptions of no nonadditive effect. The pattern of age trends was inconsistent. However, when significant there was a decrease in heritability with advancing age. These findings suggest that adult body size, shape, and composition are highly heritable in both women and men, although a decreasing tendency is seen with advancing age.

Allelic Variation in the Serotonin Transporter Gene-Linked Polymorphic Region (5-HTTLPR) and Cardiovascular Reactivity in Young Adult Male and Female Twins of European-American Descent

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. 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. 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. 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.

Factors associated with exercise lifestyle--a study of monozygotic twins.

Regular exercise is widely advocated for a broad range of health issues. Yet, the association of familial factors (i. e. both genetic and childhood environmental factors) and specific environmental factors (not shared by family members) as well as health behavior with lifelong exercise participation is currently poorly understood. A total of 117 monozygotic male twin pairs aged 35 - 69 y (mean age 49 y), recruited from the population-based Finnish Twin Cohort, were studied. A summary outcome exercise variable was created by calculating the mean hours of exercise per week from 18 y of age to present from data provided from a structured interview. Suspected factors associated with exercise were analyzed with linear regression, while pairwise relationships were analysed using polychoric correlations and structural equation modeling. There was substantial familial aggregation in adulthood exercise, accounting for 43 % of all variation in exercise using the LISREL model. Factors associated with enhanced adherence to exercise in adulthood were participation in exercise and competitive sports in adolescence (from age 12 to 18). Education, age, number of chronic diseases, smoking, alcohol use, marital status, number of children and number of changes in residence were not associated with exercise adherence in adulthood. Our results suggest that early childhood environmental factors strongly influence exercise level throughout the lifespan. Therefore, interventions aimed at enhancing lifelong exercise participation may achieve more beneficial long-term results by targeting families and other childhood and adolescent environments.

Genetic variation at the adipsin locus and response to long-term overfeeding.

The role of adipsin and adipsin Hinc II polymorphisms on the metabolic and body composition changes in response to overfeeding was studied. A total of 12 pairs of male monozygotic twins ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The preoverfeeding plasma adipsin concentration correlated positively with the change in CT-measured abdominal total and subcutaneous (P<0.05) fat. The changes in abdominal total fat and abdominal subcutaneous fat correlated negatively with changes in plasma adipsin concentrations (P<0.005). Overfeeding induced greater increases in body weight, fat mass, abdominal total and subcutaneous fat (P<0.05) in 6.1 kb noncarriers (n=10) than in 6.1 kb carriers (n=14) of the adipsin Hinc II polymorphism. The 6.1 kb noncarriers had a greater increase in plasma leptin levels (P<0.01). Also the total (P<0.01) and very-low-density lipoprotein (VLDL)-triglycerides (P<0.05), apolipoprotein B (P<0.05) and VLDL-cholesterol (P<0.05) levels increased more in the 6.1 kb noncarriers than in the 6.1 kb carriers. Adipsin plasma level could be a predictor of the changes in abdominal subcutaneous fat during times of increased energy intake. However, a greater increase in the abdominal subcutaneous fat was related to a lower increase in the plasma adipsin level. The adipsin Hinc II 6.1 kb allele noncarriers gained more abdominal subcutaneous fat and had a greater increase in plasma levels of leptin- and triglyceride-rich lipoproteins when exposed to a long-term positive energy balance. These findings provide new information on the role of adipsin on individual differences in response to chronically elevated food intake.

Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability

This longitudinal study used the full twin model to estimate change and stability of genetic contributions to morphology of two brain structures, the corpus callosum and lateral ventricles. The 142 subjects were 34 monozygotic (MZ) and 37 dizygotic (DZ) elderly male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study who underwent brain magnetic resonance imaging twice, separated by a 4-year interval. Genetic factors accounted for a substantial portion of individual differences in the size of the corpus callosum and its substructures and of lateral ventricular size. Longitudinal genetic analyses revealed no significant change in the heritability of these structures and no evidence for new genetic variance at Time 2 not present at Time 1. However, both the callosal and ventricular measures showed evidence for new environmental variance at Time 2 not present at Time 1. Confirming a previously posed hypothesis, the phenotypic correlation between absolute change in height of the corpus callosum and absolute change in ventricular volume was significant. Bivariate genetic analysis estimated a significant genetic correlation between the changes in these two structures and the genetic variance in the change of callosal height was entirely due to genes involved in the expansion of ventricles. Genetic stability was present even in old age when brain and other morphological changes can be rapid and highly variable across individuals, inconsistent with an hypothesis that random DNA damage is the cause of aging.

Deficits in Reciprocal Social Behavior in Male Twins: Evidence for a Genetically Independent Domain of Psychopathology

Previous studies have demonstrated substantial genetic influences on many child psychiatric disorders, including autism. In this study the authors attempted to quantify the degree to which genetic influences on deficits in reciprocal social behavior (a defining feature of pervasive developmental disorders) are shared with genetic influences on other domains of behavior in children. Child Behavior Checklists (CBCL) and Social Responsiveness Scales (SRS) were completed for an epidemiological sample of 219 pairs of male twins. The SRS (formerly known as the Social Reciprocity Scale) is a measure of social impairment that distinguishes children with autism spectrum disorders from those with other child psychiatric disorders. Regression analysis indicated that CBCL syndromes account for 43% of the variance in SRS scores. Bivariate analyses revealed that SRS scores are affected, in part, by phenotypic influences from the CBCL Social Problem syndrome. Forty-four percent of the causal influences on SRS scores, however, are independent from those on CBCL syndromes and are genetic in nature (90% confidence interval: 0.38-0.49). These results support the existence of a continuous distribution of deficits in reciprocal social behavior in the population, which are substantially genetically independent from other domains of child psychopathology.

Associations between back pain history and lumbar MRI findings.

Retrospective monozygotic twin cohort study. Our goal was to investigate the associations between different spinal MRI findings and current, past year, and lifetime low back pain after adjusting for occupational physical loading, smoking, genetics, and early family influences. The role of spinal pathology in back symptoms continues to be controversial. The study participants consisted of 115 monozygotic male twin pairs 35 to 69 years of age. The qualitatively assessed MRI parameters were as follows: disc height, bulging, herniations, anular tears, osteophytes, spinal stenosis, and endplate changes. Signal intensity was measured quantitatively. After controlling for age, disc height was associated with all back pain variables studied and anular tears with LBP frequency and intensity during the 12 months before imaging. Both were associated with lifetime frequency of low back pain interfering with daily activities, disability, and intensity of the worst lifetime pain episode. Other MRI findings did not explain the various symptom histories. Adjusting for physical loading in the past 12 months increased the associations of anular tears and "low back pain today" and 12-month low back pain parameters. After controlling for genotype and other familial influences, the within-pair differences in disc height and anular tears accounted for 6% to 12% of the total variance in the within-pair differences of low back pain variables. These findings raise new questions about the underlying mechanisms of LBP. The sensitivities of the only significant MRI parameters, disc height narrowing and anular tears, are poor, and these findings alone are of limited clinical importance.

A study of depressive symptoms and smoking behavior in adult male twins from the NHLBI twin study.

Self-report measures of depressive symptoms, such as the Center for Epidemiological Studies-Depression Scale (CES-D), correlate with current and lifetime smoking status. In one previous study of adult female twins, genetic factors accounted for the covariation of liability to a diagnosis of major depressive disorder and liability to lifetime smoking (Kendler, Neale, MacLean, Heath, Eaves, & Kessler, 1993b, Archives of General Psychiatry, 50, 36-43); however, it remained unclear whether genetic effects also account for the covariation between subclinical depressive symptomology and smoking behavior. In this study, we use twin structural equation modeling to explore whether genetic and/or environmental influences contribute to the covariation between depressive symptoms, as measured by the CES-D, and current and lifetime smoking status among 120 monozygotic and 114 dizygotic Caucasian male twin pairs (aged 59-69). In this sample, depressive symptoms showed small but significant correlations with current and lifetime smoking status. Univariate twin analyses indicated that additive genetic and non-shared environmental factors contributed significantly to liability to current and lifetime smoking. However, the majority of variance in CES-D scores was attributable to non-shared (individual) environment. In bivariate analyses, non-shared environmental factors accounted for the majority of covariation between liability to depressive symptoms (CES-D scores > or = 8; above the 75th percentile) and liability to current and lifetime smoking status. Taken together with the previous literature, these results suggest that the etiology of covariation among depressive symptoms and smoking behavior may vary by measurement and severity of depressive symptomology.

The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit

The magnitude of the association between nicotine withdrawal and failed smoking cessation remains uncertain, and the potential genetic contribution to that relationship is unknown. We used a twin design study to test if genetic and environmental risk factors contribute to nicotine withdrawal and failed cessation. We then estimated the magnitude of genetic and environmental risk factors and the associated correlations. Cigarette consumption data were obtained in 1992 from 4,112 (1,806 pairs, 496 singletons) male twin pairs from the Vietnam Era Twin Registry. Participants responded to a telephone administration of the Diagnostic Interview Schedule. Odds ratios were computed for failed smoking cessation as a function of 12 individual nicotine withdrawal symptoms. Genetic model fitting was performed on a sample of 1818 twin pairs, all of whom were lifetime smokers; both twins of the pairs had made at least one quit attempt. After adjustment for cigarette consumption, odds of failed smoking cessation ranged from.87 (95% CI.76-.99) for "increased appetite/weight gain" to 1.85 (95% CI 1.55-2.22) for "depressed." Genetic influences accounted for 54% and 29.7% of the variance in risk for failed smoking cessation and nicotine withdrawal, respectively. The correlation between genetic influences was significant (r=.31, 95% CI.17-.45). The magnitude of the association between failed cessation and nicotine withdrawal varied by symptom. The risk of experiencing nicotine withdrawal after a quit attempt was related partly to genetic vulnerability; lifetime risk for both failed cessation and nicotine withdrawal was related partly to genetic factors that were correlated.

Occupational driving and lumbar disc degeneration: a casecontrol study

Back problems are reported more by occupational drivers than by any other occupational group. One explanation is that whole-body vibration caused by the vehicle leads to accelerated disc degeneration, herniation, and associated symptoms. We aimed to investigate the effects of lifetime driving exposure on lumbar disc degeneration in monozygotic twins with very different histories of occupational driving during their life. We assessed 45 male monozygotic twin pairs from the population-based Finnish Twin Cohort who had greatly different patterns of occupational driving during their life. Data were obtained for driving exposures and potential confounding factors through an extensive, structured interview. We assessed disc degeneration with lumbar MRI. Disc degeneration did not differ between occupational drivers and their twin brothers. We also did not identify any overall tendency for greater degeneration or pathology in occupational drivers than their twin brothers. Although driving may exacerbate symptoms of back problems, it does not damage the disc. Our inability to identify structural damage should be encouraging to those employed in occupations involving motorised vehicles and operation of heavy equipment.

Quantitative genetic modeling of regional brain volumes and cognitive performance in older male twins

As part of an ongoing longitudinal twin study, data from both MRI brain scanning and from neuropsychological testing were obtained from 139 male–male twin pairs (72 monozygotic [MZ] and 67 dizygotic [DZ]), 69–80 years old at the time of examination. For descriptive purposes, we examined the MZ and DZ intraclass correlations (ICC) of four lobar brain volumes (frontal, temporal, parietal, and occipital), two cerebrospinal fluid (CSF) volumes (lateral ventricle and temporal horn of the lateral ventricles), and two measures of cognitive functioning (verbal memory and executive function). We found that for lobar brain and CSF space volumes, the MZ ICC were significantly greater than zero ( r=0.37–0.77) and greater than the corresponding DZ correlations ( r=0.02–0.49). Similarly, within-pair correlations for the two neuropsychological factors were statistically significant and significantly larger in MZ twin pairs than in DZ pairs, suggesting the presence of genetic variance. Bivariate genetic analysis revealed that while close to 60% of individual differences in neuropsychological performance were due to genetic influences, less than 50% of genetic effects were in common with those influencing brain volumes. These data may shed light on the genetic liability for brain diseases that affect the elderly.

The NAS-NRC Twin Registry of WWII military veteran twins. National Academy of Sciences-National Research Council.

The NAS-NRC Twin Registry is one of the oldest, national population based-twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917-1927 (inclusive) both of whom served in the armed forces. The registry, which has been in operation more than 30 years, has collected data from a variety of sources. Records-based, computerized data have come largely from the Department of Veterans Affairs, and there have been three major epidemiologic questionnaires, undertaken roughly every 15 years. Classic twin studies on a variety of medical conditions were the early focus of the registry, which now has a strong focus on chronic disease epidemiology. Work on a DNA specimen bank has been proceeding slowly, but is now a top priority, due to the increasing force of mortality in this twin cohort.

The NAS-NRC Twin Registry of WWII Military Veteran Twins

The NAS-NRC Twin Registry is one of the oldest, national population based-twin registries in the United States. It consists of 15,924 white male twin pairs born in the years 1917–1927 (inclusive) both of whom served in the armed forces. The registry, which has been in operation more than 30 years, has collected data from a variety of sources. Records-based, computerized data have come largely from the Department of Veterans Affairs, and there have been three major epidemiologic questionnaires, undertaken roughly every 15 years. Classic twin studies on a variety of medical conditions were the early focus of the registry, which now has a strong focus on chronic disease epidemiology. Work on a DNA specimen bank has been proceeding slowly, but is now a top priority, due to the increasing force of mortality in this twin cohort.

The epigenesis of planum temporale asymmetry in twins.

Variation in hemispheric asymmetry of the planum temporale (PT) has been related to verbal ability. The degree to which genetic and environmental factors mediate PT asymmetry is not known. This study examined the heritability for planar asymmetry in 12 dizygotic (DZ) and 27 monozygotic (MZ) male twin pairs who were between 6 and 16 years of age. There was weak but positive evidence for heritability of planar asymmetry. Co-twin similarity for planar asymmetry and Sylvian fissure morphology increased when excluding twins discordant for writing hand and when excluding twins exhibiting birth weight differences >20% from the analyses. Birth weight differences were also related to twin differences in total cerebral volume, but not central sulcus asymmetry. These results suggest that exogenous perinatal factors affect the epigenesis of planar asymmetry development.