Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

Development and heritability of subcortical brain volumes at ages 9 and 12.

Subcortical brain structures are involved in a variety of cognitive and emotional functions and follow different trajectories of increase and decrease in volume from childhood to adulthood. The heritability of development of subcortical brain volumes during adolescence has not been studied comprehensively. In a longitudinal twin study, we estimated to what extent subcortical brain volumes are influenced by genetic factors at ages 9 and 12. In addition, we assessed whether new genes are expressed at age 12 and whether there is evidence for genotype by sex interaction. Brain scans were acquired for 112 and 89 twin pairs at 9 and 12 years of age. In both boys and girls, there was an increase in volumes of the thalamus, hippocampus, amygdala and pallidum, and a decrease in volumes of the caudate and nucleus accumbens. The putamen showed a decrease in boys bilaterally and an increase in girls in the left hemisphere. Heritability was high (>50%) for all structures - except for the left nucleus accumbens - with heritabilities ranging from 0.50 to 0.91 at age 9, and from 0.59 to 0.88 at age 12. There were no significant new genetic effects coming into play at age 12, and there was no evidence for genotype by sex interactions. These findings suggest that despite their sensitivity to environmental effects, the heritability of subcortical brain structures is high from childhood on, resembling estimates found in adult samples.

Genome-wide association study reveals a complex genetic architecture underpinning-induced CYP3A4 enzyme activity.

Atypical cytochrome P450 3A4 (CYP3A4) enzyme activity-induced and inhibited-is thought to be the driver of numerous poor or adverse therapeutic responses to up to 50 % of all commonly prescribed drugs. We carried out a genome-wide association study to identify common genetic variants associated with variation in induced CYP3A4 activity. A total of 310 twins were included in this study. Each participant had already completed a 14 days course of St John's Wort to induce CYP3A4, which was quantified through the metabolic ratio of exogenous 3-hydroxyquinine to quinine. We failed to detect any genome-wide significant associations (P < 1 × 10(-8)) with variation in induced CYP3A4 activity although several genomic regions were highlighted which may play minor roles. We report the first GWAS of variation in induced CYP3A4 activity and our preliminary results indicate a complex genetic architecture underpinning induced CYP3A4 enzyme activity.

Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.

Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.

Familial hypobetalipoproteinemia: early neurological, hematological, and ocular manifestations in two affected twins responding to vitamin supplementation.

Familial hypobetalipoproteinemia is a disorder of lipid metabolism characterized by extremely low plasma levels of apolipoprotein B as well as low levels of total and low-density lipoprotein cholesterol. We report the case of impairment of retinal function and diffuse pain in both legs often related to physical activity, as well as the presence of acanthocytosis on peripheral blood smear. Neurophysiological studies suggested dysfunction of the thin myelinated (A) and unmyelinated (C) fibers, in spite of preserved A fiber function, which has not been previously described in this condition. All clinical symptoms and the neurophysiological abnormalities improved after high-dose vitamin E and A supplementation. These findings suggest that this syndrome may have a wide spectrum of manifestations and an early appearance of symptoms in the pediatric age group.

Genetics of coffee consumption and its stability.

BACKGROUND: Coffee is a highly popular drink associated with the pathogenesis of several diseases and the use of tobacco and alcohol. Considering the worldwide consumption, coffee has a substantial effect on individual wellbeing and public health. The role of genetic factors contributing to interindividual differences and their stability in coffee use is not well known. AIMS: We analysed the heritability of coffee consumption and its stability in a large population-based sample of Finnish twins. DESIGN: In 1975 and 1981 a postal questionnaire on coffee consumption was sent to all Finnish same-sex twin pairs born before 1958. Responses were obtained from 10 716 complete twin pairs in 1975 (3409 monozygotic and 7307 dizygotic), of whom 8124 also responded in 1981. The data were analysed using classical twin modelling based on linear structural equations. FINDINGS: Additive genetic and unique environmental factors affected coffee drinking, whereas shared environmental factors did not show any effect. Heritability of coffee consumption, adjusted for age and sex, was estimated as 0.56 in 1975 and 0.45 in 1981. Coffee consumption showed a moderate correlation between these two time-points (r = 0.58 in men and 0.55 in women). Genetic factors affecting coffee consumption were stable: additive genetic correlations were 0.84 in men and 0.83 in women, whereas unique environmental correlations were moderate (0.45 and 0.36). Additive genetic factors had the highest contribution in young adults. CONCLUSIONS: Coffee consumption is affected by both additive genetic and unique environmental factors, each of which plays an almost equally important role. The long-term stability of coffee consumption is affected mainly by a stable set of additive genetic factors.

Genetic and environmental influences on plasma homocysteine: results from a Danish twin study.

BACKGROUND: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms. METHODS: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts. RESULTS: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance. CONCLUSIONS: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.

Beliefs and practices concerning twins, hermaphrodites, and albinos among the Bamana and Maninka of Mali.

The Bamana and Maninka of Mali greatly value twins, and have elaborated a range of cultural beliefs and practices to assure their survival. Rates of twinning among these two ethnic groups average from 15.2/1000 to 17.9/1000 births compared to 10.5/1000 births (without assisted reproduction) in the United States and Great Britain. Twins (flaniw) are regarded as extraordinary beings with unusual powers, and as a gift from the supreme deity. A small altar (sinzin) is maintained in the home of twins, and periodic sacrifices of chicken blood, kola nuts, millet paste and millet beer regularly made to assure their protection. Albinos (yéfeguéw) and true and pseudo-hermaphrodites (tyéténousotéw) are also considered twin beings. However, they are believed to be the result of aberrant parental social behavior. The Bamana and Maninka believe that all four groups (twins, albinos, hermaphrodites, and pseudo-harmaphrodites) are closely linked to Faro, an androgynous supernatural being who provides equilibrium in the world. Faro is the original albino and hermaphrodite who gave birth to the first pair of twins after self-impregnation. Whenever a twin dies, a small wooden statue is sculpted called a flanitokélé (twin that remains). This commemorative figure is kept close to the surviving twin, reflecting a belief in the inseparability of twins. Eventually, the surviving twin takes responsibility for the figure. When a surviving twin marries, another figure is often sculpted in the opposite sex from the deceased twin, and placed with the original sculpture. Such commemorative sculptures are not created upon the death of those who are albinos, hermaphrodites, or pseudo-hermaphrodites. In recent years, transformational belief patterns have evolved as increasing numbers of Bamana and Maninka embrace Islam. Traditional beliefs are often given Islamic myths of origin. However, even in this Islamic context, many practices that assure twin survival are maintained.

Self-transcendence as a measure of spirituality in a sample of older Australian twins.

Measures of self-transcendence, physical health and psychological well-being were included in a self-report Health and Lifestyle questionnaire administered to Australian twins aged over 50 between 1993 and 1995. Self-transcendence appears to be higher among older Australian women than men, and was significantly associated with religious affiliation, marital status (in women) and age (in men). No strong correlations were observed between self-transcendence and any measure of psychological or physical health. Additive genetic effects were found to be important in influencing self-transcendence, with heritability estimates of 0.37 and 0.41 for men and women respectively, whilst shared environment effects were not found to be significant. Multivariate modelling of self-transcendence scores and self-reported church attendance behavior indicated substantially different etiologies for these variables, with implications for methods of investigation of religiosity and spirituality.

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study.

BACKGROUND: Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. METHODS: This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). RESULTS: While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. CONCLUSIONS: Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.

Lessons from twins: of nature, nurture, and consciousness.

Once accorded a high place in the world's mythologies, twins may be poised to reappear with new power in the images are archetypal patterns that shape the modern mind. On a concrete level, they are influencing how we define ourselves. As a result of intrauterine ultrasound studies, we are finding that more of us are twins than we ever imagined: a phenomenon dubbed "the twin without." We are also learning about within": our complementary "solar" and "lunar" traits of which the ancient Twin myths speak, whose integration is one of life's great tasks. Some of the most compelling messages of twins are appearing in an unexpected area: modern science. One of the great discoveries of 20th-century physics is the principle of complementarity: the idea that a subatomic particle can possess dual or twin aspects; that under certain experimental conditions it can manifest as a particle, and under others a wave. This is an expression of what could be called the "Twinship Principle" in modern science. The gene-environment relationship, which we have examined, is another. We might also add the predator-prey relationship in ecology; the alternation of day and night and the seasons; the sleep-wake cycle; perhaps even the one-and-zero relationship that is the basis of modern computer languages. In art, we find twinship in figure and ground, light and shade. Perhaps the most profound expressions of the Twinship Principle occur in psychology and spirituality: mind that is both local and nonlocal; the personal and the transpersonal; mortal and immortal; physical and immaterial; transcendent and immanent; sacred and profane. In all of these relationships, the entities illustrate the "coincidence of opposites." Like the poles of a magnet, they define each other and cannot exist without each other. Philosopher Alan Watts once said that the most profound metaphysical principle is that every inside has an outside, and every outside an inside. Is this the most important lesson of twins?

The consumption of tobacco, alcohol, and coffee in Caucasian male twins: a multivariate genetic analysis.

Despite the fact that epidemiologic studies demonstrate a consistent covariation between the use of tobacco, alcohol, and coffee, most previous behavioral genetic-studies have determined the contribution of genetic and environmental influences as if the consumption of these substances occurred independently of each other. In this study, we used multivariate structural equation modeling to determine the genetic and environmental overlap in the observed correlations between tobacco smoking and alcohol and coffee drinking in 173 monozygotic and 183 dizygotic male twin pairs (M age = 59 years; range = 52-66 years) who participated in a follow-up cardiovascular examination of the National Heart, Lung, and Blood Institute's Twin Study. Consistent with hypothesized psychoneurogenetic predispositions for the joint use of these substances, the most parsimonious model fitting these data identified a common genetic latent factor underlying the observed associations between smoking, alcohol, and coffee use in this cohort. This factor, herein called polysubstance use, underscores the role of genetic influence on the clustering of these behaviors in the same individual.

Heritability of substance use in the NAS-NRC Twin Registry.

This study examines the heritability of cigarette smoking, alcohol, and coffee consumption in 4,960 adult, male twin pairs (2,390 MZ and 2,570 DZ pairs) participants in an epidemiologic survey of the NAS-NRC Twin Registry conducted in the USA during 1972-73. Heritability estimates for smoking, alcohol and coffee use were calculated both before and after adjustment for shared variance between these behaviors and other demographic characteristics including socioeconomic status and an occupational adjustment score. The objective of the analysis was to determine the impact of adjustment for covariates on heritability estimates of smoking, alcohol and coffee use. Before adjustment, genetic effects in smoking, alcohol and coffee use accounted for 53%, 36%, and 45% of the variance, respectively. After adjustment, the corresponding estimates were 35%, 29%, and 36%. The fact that these estimates remained significant after adjustment for covariates leads to increased confidence about the role of genetic factors in substance use behaviors.