Differences In Twin Pairs Research Articles

Maladaptive personality traits and older adult relationship satisfaction: A co-twin control approach to understanding associations.

Maladaptive personality traits have been implicated in romantic relationship dissatisfaction, but the etiology of those links and the degree to which they extend to other types of relationships are unclear. The purpose of this study was to examine associations between maladaptive personality traits and satisfaction in various relationships using a co-twin control design to identify potential environmental contributions. The sample consisted of 1340 older adult twin participants from the Minnesota Twin Registry (Mage = 70.3) that completed the Personality Inventory for DSM-5 Faceted Brief Form and Network of Relationships Inventory (Revised for Older Adults). Several maladaptive personality traits were phenotypically associated with relationship dissatisfaction, with detachment and negative affect having the largest effects. Further, within twin pair differences in detachment and negative affect were associated with greater relationship dissatisfaction, suggesting that observed associations were mediated partly by the unique environment, not solely the result of genetic and familial confounding. Both phenotypic and co-twin associations were strongest overall in the romantic partner relationship. These findings support the notion that maladaptive personality traits are implicated in interpersonal dysfunction across multiple domains.

WITHIN TWIN PAIR DIFFERENCES INDICATE GENETIC EFFECTS OF SES INDICATORS ON LONGITUDINAL CHANGES IN PHYSICAL AGING

Abstract Socioeconomic status (SES) predicts change in health status over age, even after accounting for measured confounders such as environmental and biological risk factors. Nonetheless, the source of SES-health associations continues to be heavily debated. Twin studies offer a method for testing causal hypotheses by incorporating within and between twin pair differences in longitudinal latent growth curve models (LGCM) of physical aging on both level of functioning and rate of change with age. Three longitudinal twin studies of aging from the Swedish Twin Registry (N = 2059) included up to 27 years of follow-up on a Functional Aging Index (FAI) consisting of lung function, grip strength, walking speed, and self-report sensory functioning. SES indicators included education, financial strain, and occupation. Pair means (between family effect) and within pair differences (within family effect) were included as covariates of both intercept and slopes in a two-slope LGCM (intercept at age 75); models were corrected for sex and parental SES. LGCM results were compared across full sample, monozygotic twins, and dizygotic twins. For the FAI intercept, MZ within pair effects in all SES variables were strongly attenuated, indicating genetic confounding. For slope 1, only MZ within pair effect for education was attenuated, and no SES indicators were related to rate of change in FAI after age 75. Thus, results suggest shared genetic factors explain the association between education and change in physical aging in early aging processes. In other words, genes that impact educational achievement may also influence health behaviors and physical aging.

A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder

White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD. Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits. Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A= 0.80, 95% CI [0.57, 1.02]; A= 0.80 [0.55, 1.04]) and twins concordant for having ASD (A= 0.71 [0.33, 1.09]; A= 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule. White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work.

Genetically identical twin-pair difference models support the amyloid cascade hypothesis.

The amyloid cascade hypothesis has strongly impacted the Alzheimer's disease research agenda and clinical trial designs over the past decades, but precisely how amyloid-β pathology initiates the aggregation of neocortical tau remains unclear. We cannot exclude the possibility of a shared upstream process driving both amyloid-β and tau in an independent manner instead of there being a causal relationship between amyloid-β and tau. Here, we tested the premise that if a causal relationship exists, then exposure should be associated with outcome both at the individual level as well as within identical twin-pairs, who are strongly matched on genetic, demographic and shared environmental background. Specifically, we tested associations between longitudinal amyloid-β PET and cross-sectional tau PET, neurodegeneration and cognitive decline using genetically identical twin-pair difference models, which provide the unique opportunity of ruling out genetic and shared environmental effects as potential confounders in an association. We included 78 cognitively unimpaired identical twins with [18F]flutemetamol (amyloid-β)-PET, [18F]flortaucipir (tau)-PET, MRI (hippocampal volume) and cognitive data (composite memory). Associations between each modality were tested at the individual level using generalized estimating equation models, and within identical twin-pairs using within-pair difference models. Mediation analyses were performed to test for directionality in the associations as suggested by the amyloid cascade hypothesis. At the individual level, we observed moderate-to-strong associations between amyloid-β, tau, neurodegeneration and cognition. The within-pair difference models replicated results observed at the individual level with comparably strong effect sizes. Within-pair differences in amyloid-β were strongly associated with within-pair differences in tau (β = 0.68, P < 0.001), and moderately associated with within-pair differences in hippocampal volume (β = -0.37, P = 0.03) and memory functioning (β = -0.57, P < 0.001). Within-pair differences in tau were moderately associated with within-pair differences in hippocampal volume (β = -0.53, P < 0.001) and strongly associated with within-pair differences in memory functioning (β = -0.68, P < 0.001). Mediation analyses showed that of the total twin-difference effect of amyloid-β on memory functioning, the proportion mediated through pathways including tau and hippocampal volume was 69.9%, which was largely attributable to the pathway leading from amyloid-β to tau to memory functioning (proportion mediated, 51.6%). Our results indicate that associations between amyloid-β, tau, neurodegeneration and cognition are unbiased by (genetic) confounding. Furthermore, effects of amyloid-β on neurodegeneration and cognitive decline were fully mediated by tau. These novel findings in this unique sample of identical twins are compatible with the amyloid cascade hypothesis and thereby provide important new knowledge for clinical trial designs.

Association between PTSD and Cognitive Performance: A Longitudinal Twins Study

AbstractBackgroundPosttraumatic Stress Disorder (PTSD) is a chronic psychiatric condition that develops after exposure to life‐threatening events. The negative impact of PTSD on a person’s emotions and behavior can have long‐term deleterious effects on cognitive performance. The association between PTSD and cognition however can be confounded by unmeasured factors such as shared genetic and environmental factors. Twin studies allow us to explore this potential causal pathway by controlling for genetic and familial confounding.MethodsWe examined 77 male monozygotic and 47 dizygotic twin pairs from the Vietnam Era Twin Registry in two examinations approximately 12 years apart. At both visits, we obtained information regarding demographic data, medical history, diagnosis of PTSD and cognitive tests. Memory and learning were measured by Trail making tests, Wechsler Memory Scale (Immediate and Delayed Memory tests and Visual Reproductive Test). Linear mixed‐effect regression models were used to examine the association between PTSD and cognitive tests accounting for twin pairing. Analysis was performed by treating twins as individuals and considering within twin pair differences (among twin pairs discordant for PTSD).ResultsThe mean age was 55 years (SD 3.0) at baseline, 96% were White, and 60% monozygotic twins. Lifetime history of PTSD was not associated with cognitive measures at baseline. At follow‐up, the mean age was 67.9 years (SD 2.5). In twins considered as individuals lifetime history of PTSD was associated with worse performance on Trails A (β = 4.9, 95% CI 8.6, 1.3, p‐value = 0.008) and Trails B (β = 14.6, 95% CI 26.8, 2.4, p‐value = 0.019). After adjusting for demographics, cardiovascular and behavioral risk factors, these associations persisted (Trails A, β = 5.4, 95% CI 9.4, 1.4, p‐value = 0.009; Trails B, β = 14.1, 95% CI 26.9, 1.2, p‐value = 0.032). The within‐pair estimates were similar to individual estimates. There was no association with Wechsler immediate or delayed story recall or Visual Reproductive Test. In stratified analyses, the results were similar by zygosity.ConclusionsLifetime history of PTSD is associated with poor cognitive performance, primarily in the executive function domain, which manifests at older age. This association is not confounded by shared genetic and other familial factors.

872Novel approach to estimating sex differences unconfounded by familial factors from studying male-female twin pairs

Abstract Focus of Presentation Males and females differ substantially in their exposures and outcomes across the life-course. Previous research into sex differences has been limited by an inability to account for inter-individual differences in genetic factors and in their early-life environment. Studying within male-female twin pair differences offers a unique opportunity to address these weaknesses that has not yet been exploited. Findings We studied linked health administrative data for 28,054 newborn Brazilian male-female twin pairs. Using random-effects logistic regression, we found that males had 1.61 (95% CI: 1.38– 1.90, P&amp;lt;0.001) times higher risk of early neonatal mortality (first 6 days of life) compared with their female co-twins, after adjusting empirically for birthweight and matching for gestational age and, by design, for unmeasured familial factors including on average 50% of genetic factors. From analysing within-pair differences in genome-wide DNA methylation in blood samples for 55 Australian adolescent male-female twin pairs, we found that 1,227 DNA methylation sites were more methylated in females while only 157 sites were more methylated in males (P&amp;lt;10-6). We also found weak evidence suggesting that males have older DNA-methylation-based biological age than females (P=0.2). Conclusions/Implications Sex differences not explained by familial confounders exist for neonatal mortality in newborns and for DNA methylation in blood during adolescence. Key messages Analysing the within-pair differences of male-female twin pairs brings novel and important strengths to the study of sex differences, helping mitigate bias from uncontrolled familial confounding caused by genetic and environmental factors.

Middle-age dementia risk scores and old-age cognition: a quasi-experimental population-based twin study with over 20-year follow-up

BackgroundMiddle-age risk scores predict cognitive impairment, but it is not known if these associations are evident when controlling for shared genetic and environmental factors. Using two risk scores, self-report educational-occupational...

Plasma homocysteine concentrations and depression: A twin study.

Homocysteine is an amino acid formed during metabolism of the essential amino acid methionine that plays an important role in energy metabolism and neurotransmitter synthesis. High levels of homocysteine have been linked to both depression and cardiovascular disease, however studies of depression have not always been consistent, possibly related to differences in methodology among studies. The study of twins in clinical research can be useful in controlling for confounding factors. The purpose of this study was to assess the relationship between depression and plasma homocysteine in a study of twins. Homocysteine concentration was assessed in twins (N = 202) from the Vietnam Era Twin Registry, including twin pairs discordant for the diagnosis of Major Depressive Disorder (MDD) and twin pairs without MDD. Self reported depressive symptom levels were also measured as a continous variable using the Beck Depression Inventory (BDI). The average homocysteine concentration was 7.9 μmol/L (2.1 μmol/L SD, range of 2.0-17.1 μmol/L). There were no within twin pair differences in homocysteine concentration within twin pairs discordant for MDD and within twin pairs that differed for BDI score. There was a significant pair-level relationship between depressive symptoms as measured by mean BDI score and homocysteine concentration, such that the higher the mean BDI score of the twin pair, the higher the mean homocystein of the pair (p < .001). Every 10 point increase in BDI score was associated with an 0.8 μmol/L increase in homocysteine concentration at the pair level. These findings are not consistent with a causal role for elevated homocysteine in the development of depression, but rather point to familial confounding or other factors that are shared by twin brothers and that contribute to both depression and homocysteine levels.

Genetic and environmental influences on corticostriatal circuits in twins with autism

Corticostriatal circuits (CSC) have been implicated in the presentation of some restricted and repetitive behaviours (RRBs) in children with autism-spectrum disorder (ASD), and preliminary evidence suggests that disruptions in these pathways may be associated with differences in genetic and environmental influences on brain development. The objective of this investigation was to examine the impact of genetic and environmental factors on CSC regions in twins with and without ASD and to evaluate their relationship with the severity of RRBs. We obtained T1-weighted MRIs from same-sex monozygotic and dizygotic twin pairs, aged 6–15 years. Good-quality data were available from 48 ASD pairs (n = 96 twins; 30 pairs concordant for ASD, 15 monozygotic and 15 dizygotic; 18 pairs discordant for ASD, 4 monozygotic and 14 dizygotic) and 34 typically developing control pairs (n = 68 twins; 20 monozygotic and 14 dizygotic pairs). We generated structural measures of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, putamen, pallidum and thalamus using FreeSurfer. Twin pair comparisons included intraclass correlation analyses and ACE modelling (a2 = additive genetics; c2 = common or shared environment; e2 = unique or nonshared environment). We also assessed correlations with RRB severity. Structural variation in CSC regions was predominantly genetically mediated in typically developing twins (a2 = 0.56 to 0.87), except for ACC white matter volume (a2 = 0.42, 95% confidence interval [CI] 0.08 to 0.77). We also observed similar magnitudes of genetic influence in twins with ASD (a2 = 0.65 to 0.97), but the cortical thickness of the ACC (c2 = 0.44, 95% CI 0.22 to 0.66) and OFC (c2 = 0.60, 95% CI 0.25 to 0.95) was primarily associated with environmental factors in only twins with ASD. Twin pair differences in OFC grey matter volume were also correlated with RRB severity and were predominantly environmentally mediated. We obtained MRIs on 2 scanners, and analytical approaches could not identify specific genetic and environmental factors. Genetic factors primarily contribute to structural variation in subcortical CSC regions, regardless of ASD, but environmental factors may exert a greater influence on the development of grey matter thickness in the OFC and ACC in children with ASD. The increased vulnerability of OFC grey matter to environmental influences may also mediate some heterogeneity in RRB severity in children with ASD.

Placental T2* estimated by magnetic resonance imaging and fetal weight estimated by ultrasound in the prediction of birthweight differences in dichorionic twin pairs

IntroductionIntertwin birthweight (BW) difference is associated with an increased risk of adverse outcome. Ultrasound estimated fetal weight (EFW) is the current method to predict intertwin BW difference, however, the sensitivity is poor. Therefore, new methods are needed. Placental T2* estimated by magnetic resonance imaging (MRI) provides non-invasive information about the placental function. This study aimed to investigate placental T2* difference as a new predictor of BW difference, and to compare it to the EFW. MethodsWe included 25 dichorionic twin pairs at 19–38 weeks’ gestation. Placental T2* was obtained by MRI and EFW by ultrasound. Correlations between each predictor and BW difference were examined by simple linear regression, and the combined model was analyzed by multiple linear regression and likelihood ratio test. ResultsStrong positive correlations were demonstrated between intertwin differences in placental T2* and BW (r = 0.80, p < 0.005), and EFW and BW (r = 0.64, p < 0.005). Placental T2* difference was a strong independent predictor of BW difference (p < 0.001), and the combined model performed better than each predictor alone (p < 0.0001). DiscussionThis pilot study demonstrates that placental T2* difference may be a predictor of intertwin BW difference irrespectively of fetal size. The clinical potential of this method deserves further investigation in a larger clinical study

Retinal and Cerebral Microvasculopathy: Relationships and Their Genetic Contributions.

Retinal microvasculopathy may reflect small vessel disease in the brain. Here we test the relationships between retinal vascular parameters and small vessel disease, the influence of cardiovascular risk factors on these relationships, and their common genetic background in a monozygotic twin cohort. We selected 134 cognitively healthy individuals (67 monozygotic twin pairs) aged ≥60 years from the Netherlands Twin Register for the EMIF-AD PreclinAD study. We measured seven retinal vascular parameters averaged over both eyes using fundus images analyzed with Singapore I Vessel Assessment. Small vessel disease was assessed on MRI by a volumetric measurement of periventricular and deep white matter hyperintensities. We calculated associations between RVPs and WMH, estimated intratwin pair correlations, and performed twin-specific analyses on relationships of interest. Deep white matter hyperintensities volume was positively associated with retinal tortuosity in veins (P = 0.004) and fractal dimension in arteries (P = 0.001) and veins (P = 0.032), periventricular white matter hyperintensities volume was positively associated with retinal venous width (P = 0.028). Intratwin pair correlations were moderate to high for all small vessel disease/retinal vascular parameter variables (r = 0.49-0.87, P < 0.001). Cross-twin cross-trait analyses showed that retinal venous tortuosity of twin 1 could predict deep white matter hyperintensities volume of the co-twin (r = 0.23, P = 0.030). Within twin-pair differences for retinal venous tortuosity were associated with within twin-pair differences in deep white matter hyperintensities volume (r = 0.39, P = 0.001). Retinal arterial fractal dimension and venous tortuosity have associations with deep white matter hyperintensities volume. Twin-specific analyses suggest that retinal venous tortuosity and deep white matter hyperintensities volume have a common etiology driven by both shared genetic factors and unique environmental factors, supporting the robustness of this relationship.

Associations between loneliness and personality are mostly driven by a genetic association with Neuroticism.

Loneliness is an aversive response to a discrepancy between desired and actual social relationships and correlates with personality. We investigate the relationship of loneliness and personality in twin family and molecular genetic data. Phenotypic correlations between loneliness and the Big Five personality traits were estimated in 29,625 adults, and in a group with genome-wide genotype data (N = 4,222), genetic correlations were obtained. We explored whether genetic correlations may reflect causal relationships by investigating within monozygotic twin pair differences (Npairs = 2,662), by longitudinal within-subject changes in personality and loneliness (N = 4,260-9,238 longitudinal comparisons), and by longitudinal cross-lagged panel analyses (N = 15,628). Finally, we tested whether genetic correlations were due to cross-trait assortative mating (Nspouse pairs = 4,436). The strongest correlations with loneliness were observed for Neuroticism (r = .55) and Extraversion (r = -.33). Only Neuroticism showed a high correlation with loneliness independent of other personality traits (r = .50), so follow-up analyses focused on Neuroticism. The genetic correlation between loneliness and Neuroticism from genotyped variants was .71; a significant reciprocal causal relationship and nonsignificant cross-trait assortative mating imply that this is at least partly due to mediated pleiotropy. We show that the relationship between loneliness and personality is largely explained by its relationship with Neuroticism, which is substantially genetic in nature.

Family Cohesion and the General Factor of Personality: Examining Differences in Monozygotic Twin Pairs

It was recently found that differences between monozygotic twins in the general factor of personality were positively correlated with differences in adulthood recollections of maternal and paternal affection. The current study used data from the Swedish Adoption/Twin Study on Aging to possibly replicate and extend these findings. The results were consistent with replication for monozygotic twin pairs who were reared together (base total of 166 pairs), but not for those who were reared apart (base total of 99 pairs). This finding suggests that the effect is due to the relative and not absolute aspects of the familial environment during childhood. Additionally, the general factor of personality was not shown to mediate childhood and adulthood family cohesion. These results suggest that the general factor of personality may have independent effects on recollections of childhood family cohesion and current family cohesion. Thus, both how family dynamics are related to the development of the general factor of personality and how the general factor of personality impacts adulthood family relations (e.g., parenting) are important areas of future inquiry.

Epigenetics in Odontogenesis and its Influences.

Odontogenesis is fundamentally controlled by the genome. However, epigenetic factors have indispensable effects during odontogenesis. Previous studies have shown that exogenous factors, such as the environment, that cause hypomethylation and hypermethylation in DNA may lead to dental differences in monozygotic twin pairs. In addition, abnormalities in epigenetic regulation could induce disruptions in odontogenesis, thereby causing tooth malformation or agenesis. This review overviews the epigenetic mechanisms involved in odontogenesis with the aim of establishing a fundamental vision of tooth development, which might be useful in further research in odontogenesis and therapy for dental diseases. We summarized articles about epigenetics in odontogenesis. Here, we present concrete epigenetic regulation mechanisms in odontogenesis that have been reported previously, following the order of microRNA, DNA methylation and histone modification. Epigenetic factors influence the proliferation, differentiation or apoptosis of cells that play indispensable roles during the process of odontogenesis which have the ability to exquisitely regulate the tooth number, size and shape.

Maternal feeding practices and fussy eating in toddlerhood: a discordant twin analysis.

BackgroundParental feeding practices are thought to play a causal role in shaping a child’s fussiness; however, a child-responsive model suggests that feeding practices may develop in response to a child’s emerging appetitive characteristics. We used a novel twin study design to test the hypothesis that mothers vary their feeding practices for twin children who differ in their ‘food fussiness’, in support of a child-responsive model.MethodsParticipants were mothers and their 16 month old twin children (n = 2026) from Gemini, a British twin birth cohort of children born in 2007. Standardized psychometric measures of maternal ‘pressure to eat’, ‘restriction’ and ‘instrumental feeding’, as well as child ‘food fussiness’, were completed by mothers. Within-family analyses examined if twin-pair differences in ‘food fussiness’ were associated with differences in feeding practices using linear regression models. In a subset of twins (n = 247 pairs) who were the most discordant (highest quartile) on ‘food fussiness’ (difference score ≥ .50), Paired Samples T-test were used to explore the magnitude of differences in feeding practices between twins. Between-family analyses used Complex Samples General Linear Models to examine associations between feeding practices and ‘food fussiness’.ResultsWithin-pair differences in ‘food fussiness’ were associated with differential ‘pressure to eat’ and ‘instrumental feeding’ (ps < .001), but not with ‘restriction’. In the subset of twins most discordant on ‘food fussiness’, mothers used more pressure (p < .001) and food rewards (p < .05) with the fussier twin. Between-family analyses indicated that ‘pressure to eat’ and ‘instrumental feeding’ were positively associated with ‘food fussiness’, while ‘restriction’ was negatively associated with ‘food fussiness’ (ps < .001).ConclusionsMothers appear to subtly adjust their feeding practices according to their perceptions of their toddler’s emerging fussy eating behavior. Specifically, the fussier toddler is pressured more than their less fussy co-twin, and is more likely to be offered food rewards. Guiding parents on how to respond to fussy eating may be an important aspect of promoting feeding practices that encourage food acceptance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12966-016-0408-4) contains supplementary material, which is available to authorized users.

G×E Interaction Influences Trajectories of Hand Grip Strength.

Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34-99 (N=10,681). Fisher's test for mixture distribution of within-monozygotic twin-pair differences (N=1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.

Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a Profile Suggestive of a Satiety Factor and Are Related to BMI.

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.

The relationship between body mass index and uric acid: a study on Japanese adult twins.

The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95% confidence interval: 0.016-0.373) in men and 0.186 (95% confidence interval: 0.071-0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95% confidence interval: 0.072-0.594) in men and 0.314 (95% confidence interval: 0.151-0.477) in women. The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

Stature and life-time labor market outcomes: Accounting for unobserved differences

We use twin data matched to register-based individual information on earnings and employment to examine the effect of height on life-time labor market outcomes. The use of twin data allows us to remove otherwise unobserved ability and other differences. The twin pair difference estimates from instrumental variable estimation for genetically identical twins reveal a significant height–wage premium for women but not for men. This result implies that cognitive ability explains the effect of height on life-time earnings for men. Additional findings using capital income as the outcome variable suggest that discrimination against short persons may play a role for women.

Monozygotic Twin Differences in Non-shared Environmental Factors Associated with Chronotype

Twin studies have highlighted that a large proportion of variability in chronotype is accounted for by individual-specific environmental factors (non-shared environmental influences). However, little research has aimed to identify specific non-shared environmental influences on chronotype. Although epidemiological studies have shed light on possible environmental influences on chronotype, a substantial amount of research has highlighted the importance of genetic influences on exposure toward specific environments, a process termed gene-environment correlation. It is possible that associations between the environment and chronotype are in part determined by genetics, rather than being purely environmental in origin. One way of exploring the contribution of purely non-shared environmental components on associations between chronotype and the environment is to use the monozygotic twin differences design. This design allows us to tease apart the influences of genetics and the environment to identify purely environmental components. One hundred eighty-nine monozygotic twin pairs (mean age 19.81 years, SD = 1.26, range = 18-22 years, 66.1% female) completed the Horne and Östberg Morningness-Eveningness Questionnaire as a measure of chronotype and questionnaires assessing the following candidate non-shared environmental influences: dependent and independent negative life events, educational attainment, employment status, relationship status, deviant peers, affiliation with deviant peers, general health, smoking, drug use, and alcohol use. Linear regression analyses indicated the presence of gene-environment correlation for the majority of associations between chronotype and candidate environmental influences. When controlling for genetic and shared environmental effects, within monozygotic twin-pair differences in chronotype were associated with within monozygotic twin-pair differences in dependent negative life events (β = -0.27, p < 0.001), educational attainment (β = -0.14, p < 0.05), smoking status (β = 0.22, p < 0.01), and drug use (β = -0.16, p < 0.01). These results suggest that some of the association between these variables is purely environmental in nature. The associations between the remaining environmental variables and chronotype, however, may be intertwined with underlying genetic factors. These findings add to our understanding of genetic and environmental mechanisms underlying the biological clock.