Discordant Twin Pairs Research Articles

Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts

BackgroundSmokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background.Methods and findingsThe international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18–69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade.ConclusionsSmoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2.

The relationship between subjective well-being and mortality within discordant twin pairs from two independent samples.

Prior research has shown robust associations between greater subjective well-being (SWB) and reduced mortality. Whether this observed association is causal in nature or due instead to confounding genetic or environmental factors affecting both SWB and mortality is not well understood. We used a combined sample of 6,802 twins drawn from two cohorts: the Longitudinal Study of Middle-Aged Danish Twins (MADT; N = 2,815, baseline age between 45 and 69 years, M = 56.8, SD = 6.4) and the Longitudinal Study of Aging Danish Twins (LSADT; N = 3,987, baseline age between 70 and 97 years, M = 76.6, SD = 4.9). The relationship between SWB, encompassing measures of life satisfaction and affect, and all-cause mortality was evaluated using survival analyses at both the individual level and within twin pairs. Twin difference analyses were completed within 1,053 monozygotic (MZ) twin pairs and 1,143 dizygotic (DZ) twin pairs to control for genetic and shared environmental confounding. As expected, the individual-level results showed that higher levels of SWB were associated with reduced mortality: affect hazard ratio (HR) = .90, 95% confidence interval (CI) [.87, .94]; life satisfaction HR = .88, 95% CI [.84, .92]. The effect of SWB on reduced mortality remained significant within both MZ and DZ pairs, suggesting that the association is independent of genetic and nonshared environmental confounding factors. These findings, which generalized across both younger (MADT) and older (LSADT) cohorts of adults, remained significant when accounting for demographic factors, physical health, and cognitive functioning. (PsycINFO Database Record

Association between obesity and DNA methylation among the 7-16 year-old twins

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

O1.4. CEREBROSPINAL FLUID FINDINGS IN TWINS WITH PSYCHOTIC SYMPTOMS – NOVEL FINDINGS AND FUTURE PROSPECTS

BackgroundSchizophrenia and bipolar disorder are severe mental disorders with unknown etiology. Our research group has studied biomarkers in the cerebrospinal fluid (CSF) of twins with schizophrenia and bipolar disorder to be able to determine the genetic and environmental influences. In brain disorders, CSF is the most appropriate substrate to study as it may reflect the brain biochemistry better than blood. In this presentation I aim to give an overview of our findings and their relation to psychotic disorders. I intend to present our most recent preliminary finding and to discuss future prospects.MethodsWe studied CSF-markers from a cohort of 50 monozygotic (MZ) and dizygotic (DZ) twins with schizophrenia or bipolar disorder. The twins have gone through diagnostic assessments and have been extensively phenotyped with questionnaires, symptom scales for psychiatric symptoms as well as neuropsychological testing. We have analyzed monoamines, microglia-, neurodegenerative-, kynurenine-, and inflammatory markers using immunoassays and high-performance liquid chromatography techniques. We have also studied microscopic structures with scanning electron microscopy.ResultsOne of our main findings was that soluble cluster of differentiation 14 protein (sCD14) was higher in twins with schizophrenia or bipolar disorder compared to their not affected co-twins. A later analysis showed that the difference within the discordant twin-pairs was higher in the DZ twin pairs (β=28697.1, t=3.20, p=0.024) compared with the MZ twin pairs (β=5577.5, t=2.10, p=0.081) suggesting that genetic components along with unique environmental effects have an influence on the higher sCD14 levels in patients with schizophrenia and bipolar disorder. We also found that sCD14 was higher in those patients with more psychotic symptoms.In our study on microscopic structures in CSF we found that the structures were prevalent not only in the patients with schizophrenia and bipolar disorder but also in their not affected co-twins. The finding suggests that genetic factors may be partly involved in the formation of the structures.DiscussionWe have analyzed inflammatory and neurodegerative markers in the CSF of twins with psychotic disorders to be able to study genetic and environmental influences. Our results indicate that sCD14 may have an influence on microglia activation in psychosis. We have continued with analyses on the correlations between all the markers, the monoamine metabolites and associations with symptoms and cognitive ability and the preliminary results from these analyses will be presented.To conclude CSF analyses for biomarkers in twins may result in extended knowledge regarding the genetic and environmental relationships. Our unique twin data gives us the possibility to study CSF-markers in relation to psychiatric symptoms and cognitive measures. For future studies it would be of interest to assemble twin-samples from several research groups to be able to study research questions regarding gene and environment interactions.

Apolipoprotein E DNA methylation and late-life disease.

BackgroundThis study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD).MethodsDNA methylation across theAPOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3′exon that also harbours theAPOE ε2 and ε4 alleles. DNA methylation levels in leukocytes were measured using the Illumina 450K array in 447 Swedish twins (mean age 78.1 years). We used logistic regression to investigate whether methylation levels in those regions affect the odds of disease.ResultsWe found that methylation levels in the promoter region were associated with dementia and AD after adjusting for sex, age at blood draw, education, smoking and relatedness among twins [odds ratio (OR) 1.32 per standard deviation increase in methylation levels, 95% confidence interval (CI) 1.08–1.62 for dementia; OR 1.38, 95% CI 1.07–1.78 for AD). We did not detect any difference in methylation levels between CVD cases and controls. Results were similar when comparing within discordant twin pairs, and did not differ as a function ofAPOE genotype.ConclusionsWe found that higher DNA methylation levels in the promoter region ofAPOE increase the odds of dementia and AD, but not CVD. The effect was independent ofAPOE genotype, indicating that allelic variation and methylation variation inAPOE may act independently to increase the risk of dementia.

Migraine with visual aura associated with thicker visual cortex.

Until recent years it was believed that migraine with aura was a disorder causing intermittent neurological symptoms, with no impact on brain structure. However, recent MRI studies have reported increased cortical thickness of visual and somatosensory areas in patients with migraine with aura, suggesting that such structural alterations were either due to increased neuronal density in the areas involved, or a result of multiple episodes of cortical spreading depression as part of aura attacks. Subsequent studies have yielded conflicting results, possibly due to methodological reasons, e.g. small number of subjects. In this cross-sectional study, we recruited females aged 30-60 years from the nationwide Danish Twin Registry. Brain MRI of females with migraine with aura (patients), their co-twins, and unrelated migraine-free twins (controls) were performed at a single centre and assessed for cortical thickness in predefined cortical areas (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The difference in cortical thickness between patients and controls adjusted for age, and other potential confounders was assessed. Comparisons of twin pairs discordant for migraine with aura were also performed. Comparisons were based on 166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence interval 0.008 to 0.067)], while differences in the remaining areas examined were not statistically significant [adjusted mean difference (95% confidence interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of interest and active migraine, or number of lifetime aura attacks. Migraine with aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039 mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a thicker cortex corresponding to visual areas and our results indicate this may be an inherent trait rather than a result of repeated aura attacks.

Integrated Analysis of Gene Expression Differences in Twins Discordant for Disease and Binary Phenotypes

While both genes and environment contribute to phenotype, deciphering environmental contributions to phenotype is a challenge. Furthermore, elucidating how different phenotypes may share similar environmental etiologies also is challenging. One way to identify environmental influences is through a discordant monozygotic (MZ) twin study design. Here, we assessed differential gene expression in MZ discordant twin pairs (affected vs. non-affected) for seven phenotypes, including chronic fatigue syndrome, obesity, ulcerative colitis, major depressive disorder, intermittent allergic rhinitis, physical activity, and intelligence quotient, comparing the spectrum of genes differentially expressed across seven phenotypes individually. Second, we performed meta-analysis for each gene to identify commonalities and differences in gene expression signatures between the seven phenotypes. In our integrative analyses, we found that there may be a common gene expression signature (with small effect sizes) across the phenotypes; however, differences between phenotypes with respect to differentially expressed genes were more prominently featured. Therefore, defining common environmentally induced pathways in phenotypes remains elusive. We make our work accessible by providing a new database (DiscTwinExprDB:http://apps.chiragjpgroup.org/disctwinexprdb/) for investigators to study non-genotypic influence on gene expression.

Supplemental Material for The Relationship Between Subjective Well-Being and Mortality Within Discordant Twin Pairs From Two Independent Samples

Supplemental Material for The Relationship Between Subjective Well-Being and Mortality Within Discordant Twin Pairs From Two Independent Samples

Birth weight, sex, and celiac disease: a nationwide twin study.

ObjectiveEarlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.Materials and methodsUsing the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.ResultsThe prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.ConclusionThis population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health.

Adverse outcomes of sick leave due to mental disorders: A prospective study of discordant twin pairs.

The aim of this study was to investigate whether sick leave due to different mental disorders increased the risk of reoccurring sick-leave, disability pension and unemployment, taking genetics and shared environment into account. This register-based cohort study contains 2202 discordant twin pairs 18-64 years old, where one twin had sick leave due to a mental disorder 2005-2006. The end of the sick-leave spell was the start of follow-up for both twins. The twins were followed up for reoccurring sick-leave, disability pension and unemployment (> 180 days in a year), until December 2012. Analyses were censored for disability pension, death, emigration and old-age pension. Cox proportional hazards models with time-varying covariates were used to calculate hazard ratios with 95% confidence intervals (CI). Those with sick leave due to mental disorders had a 3.64 (CI: 3.24-4.08) times higher risk of reoccurring sick-leave within the first two years; after that, hazard ratios were attenuated and explained by genetic factors. The first year, they had 12.24 (CI: 8.11-18.46) times the risk of disability pension. The risk was attenuated but remained at 2.75 (CI: 2.07-3.65) after one year. The risk of unemployment was 1.99 (CI: 1.72-2.31) during the whole follow-up period. The risk of unemployment and disability pension was lower for those with stress-related than other mental disorders, this was less clear for recurrent reoccuring sick-leave. Sick leave due to mental disorders increased the risk of reoccurring sick-leave within two years, disability pension and unemployment, independent of genetics and shared environment.

Work-Home Interference, Perceived Total Workload, and the Risk of Future Sickness Absence Due to Stress-Related Mental Diagnoses Among Women and Men: a Prospective Twin Study

PurposeWork-home interference has been proposed as an important explanation for sickness absence (SA). Previous studies show mixed results, have not accounted for familial factors (genetics and shared everyday environment), or investigated diagnosis specific SA. The aim was to study whether work-home interference and perceived total workload predict SA due to stress-related mental diagnoses, or SA due to other mental diagnoses, among women and men, when adjusting for various confounders and familial factors.MethodsThis study included 11,916 twins, 19–47 years (49% women). Data on work-to-home and home-to-work conflicts, perceived total workload, and relevant confounders were derived from a 2005 survey, and national register data on SA spells until 2013 were obtained. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Discordant twin pair design was applied to adjust for familial factors.ResultsEach one unit increase in work-to-home and home-to-work conflicts, and perceived total workload was associated with higher odds for SA due to stress-related mental diagnoses and to SA due to other mental diagnoses among women, when adjusting for sociodemographic factors (ORs 1.15–1.31). Including health or familial factors, no associations remained. For men, each one unit increase in work-to-home conflicts was associated with higher odds for SA due to stress-related diagnoses (ORs 1.23–1.35), independently of confounders.ConclusionWork-to-home conflict was independently associated with future SA due to stress-related diagnoses among men only. Health- and work-related factors seem to be important confounders when researching work-home interference, perceived total workload, and SA. Not including such confounders involves risking drawing incorrect conclusions. Further studies are needed to confirm sex differences and whether genetic factors are important for the associations studied.

Night work as a risk factor of future disability pension due to musculoskeletal diagnoses: a prospective cohort study of Swedish twins.

This study investigated the associations between night work, sleep and disability pension (DP) due to musculoskeletal disorders (MSD), while controlling for several confounding factors including both genetic factors and shared family background. The study sample consisted of 27 165 Swedish twin individuals born in 1935-58 with comprehensive survey data on sociodemographic, health and lifestyle factors. Night work was assessed as years of working hours at night at least every now and then, and categorized into 'not at all, 1-10 years and over 10 years'. Data on DP with MSD (ICD-diagnoses M00-M99) were obtained from the National Social Insurance Agency. Follow-up was from the time of the interview in 1998-2003 until 2013. Information on the length and quality of sleep was available for a sub-sample of twins (n = 1684). Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). During the follow-up, 1338 (5%) participants were granted DP due to MSD. Both 1-10 years (HR 1.33, 95% CI 1.17-1.53) and over 10 years of night work (HR 1.39 95% CI 1.18-1.64) increased the risk of future DP. The associations were not affected by health, lifestyle or sleep factors. In the discordant twin pair analysis, the associations between night work and DP due to MSD attenuated. Night work was associated with increased risk of DP due to MSD independently from health and lifestyle factors. Familial confounding could not be ruled out.

Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort

Purpose:Genetic contributions to tinnitus have been difficult to determine due to the heterogeneity of the condition and its broad etiology. Here, we evaluated the genetic and nongenetic influences on self-reported tinnitus from the Swedish Twin Registry (STR).Methods:Cross-sectional data from the STR was obtained. Casewise concordance rates (the risk of one twin being affected given that his/her twin partner has tinnitus) were compared for monozygotic (MZ) and dizygotic (DZ) twin pairs (N = 10,464 concordant and discordant twin pairs) and heritability coefficients (the proportion of the total variance attributable to genetic factors) were calculated using biometrical model fitting procedures.Results:Stratification of tinnitus cases into subtypes according to laterality (unilateral versus bilateral) revealed that heritability of bilateral tinnitus was 0.56; however, it was 0.27 for unilateral tinnitus. Heritability was greater in men (0.68) than in women (0.41). However, when female pairs younger than 40 years of age were selected, heritability of 0.62 was achieved with negligible effects of shared environment.Conclusion:Unlike unilateral tinnitus, bilateral tinnitus is influenced by genetic factors and might constitute a genetic subtype. Overall, our study provides the initial evidence for a tinnitus phenotype with a genetic influence.Genet Med advance online publication 23 March 2017

Exploring Subclinical Phenotypic Features in Twin Pairs Discordant for Cleft Lip and Palate.

Monozygotic twins of an individual with an orofacial cleft have a significantly elevated risk for orofacial cleft compared with the general population, but still the concordance rate for orofacial cleft in monozygotic twins is about 40% to 50%. The goal of this study was to determine whether unaffected cotwins have an increased frequency of orbicularis oris muscle defects, a subclinical form of orofacial cleft. The presence of such defects may reduce the overall rate of discordance. A total of 63 discordant monozygotic and dizygotic twin pairs, 262 unaffected nontwin siblings, and 543 controls with no history of orofacial clefts were assessed for orbicularis oris defects by high-resolution ultrasound. Frequencies were compared by the Fisher exact test. Unaffected cotwins from discordant monozygotic pairs had a higher frequency of defects (12.5%) than the other test groups (6.38% to 6.99%), but the difference was not statistically significant (P = .74). In this study, orbicularis oris defects were not statistically significantly more common among the unaffected twins from orofacial cleft discordant twin pairs. The trends in the results warrant future studies with larger sample sizes and additional subclinical phenotypes.

Social and economic consequences of alcohol use disorder: a longitudinal cohort and co-relative analysis.

Although alcohol use disorder (AUD) is associated with future risk for psychosocial dysfunction, the degree to which this arises from a direct causal effect of AUD on functioning v. from correlated risk factors (also known as confounders) is less clearly established. AUD was assessed from Swedish medical, criminal and pharmacy registries. In a large general population cohort, using Cox proportional hazard and regression models, we predicted from the onset of AUD four outcomes: early retirement, unemployment, social assistance, and individual income. We then examined the degree to which these associations were attenuated by relevant confounders as well as by the use of discordant cousin, half-sibling, full-sibling, and monozygotic twin pairs. In males, AUD most strongly predicted social assistance [hazard ratio (HR) 8.27, 95% confidence interval (CI) 7.96-8.59], followed by early retirement (HR 5.63, 95% CI 5.53-5.72) and unemployment (HR 2.75, 95% CI 2.65-2.85). For income at age 50, AUD was associated with a decrease in income of 0.24 s.d.s (95% CI -0.25 to -0.23). Results were similar in females. Modest to moderate attenuation of these associations was seen in both sexes after the addition of relevant covariates. These associations were reduced but remained robust in discordant co-relative pairs, including monozygotic twins. Our results suggest that AUD has a causal impact on a range of measures reflective of psychosocial dysfunction. These findings provide strong support for the drift hypothesis. However, some of the associations between AUD and dysfunction appear to be non-causal and result from shared risk factors, many of which are likely familial.

The association between parental separation during childhood and obesity in adulthood: a Danish twin study.

SummaryObjectiveThe purpose of this study was to examine if parental separation during childhood is associated with obesity in adulthood.MethodsA co‐twin case–control study of 146 adult same‐sexed twin pairs with discordant body mass index (BMI) (i.e. one of the twins should have a BMI of 20–25 kg/m2, and the co‐twin's BMI ≥ 30 kg/m2) was selected from Danish Twin Registry (DTR). In total of 236 eligible twin individuals participated in the study. Childhood parental separation (defined as separation from one of the biological parents, regardless of the reason for separation) for at least one year prior to age 17 was self‐reported. The statistical analysis includes logistic and linear regression models using STATA 13.0.ResultsThere were no differences in the odds of developing obesity in adulthood between the twin who stayed with a father and the co‐twin who was separated from him for at least 1 year prior to age 17 [OR = 1.22, 95%CI (0.46–3.34), p = 0.65]. Separation from a mother also showed no differences in the odds for developing obesity [OR = 0.90, 95%CI (0.32–2.46), p = 0.82].ConclusionsBecause of the limited number of discordant twin pairs for childhood parental separation, we cannot provide evidence to suggest that separation from parents in childhood was associated with developing obesity in adulthood. Further studies of pooling discordant twins from several countries should be considered.

Somatosensory Brain Function and Gray Matter Regional Volumes Differ According to Exercise History: Evidence from Monozygotic Twins.

Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34±1years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images. We obtained exercise history and measured physical fitness and body composition. Equivalent electrical dipole sources of SMMR as well as gray matter (GM) voxel counts in regions of interest indicated by source analysis were evaluated. SMMR dipolar source strengths differed between active and inactive twins within twin pairs in postcentral gyrus, medial frontal gyrus and superior temporal gyrus and in anterior cingulate (AC) GM voxel counts differed similarly. Compared to active twins, their inactive twin brothers showed greater dipole strengths in short periods of the deviant-elicited SMMR and larger AC GM voxel counts. Stronger activation in early unattended cortical processing of the deviant sensory signals in inactive co-twins may imply less effective gating of somatosensory information in inactive twins compared to their active brothers. Present findings indicate that already in 30's long-term physical activity pattern is linked with specific brain indices, both in functional and structural domains.

Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins

Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference ΔBMI ≥ 3kg/m2) and concordant (n = 5, ΔBMI < 3kg/m2) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins. Abdominal body fat distribution (MRI), liver fat content (magnetic resonance spectroscopy), insulin sensitivity (OGTT), high-sensitivity C-reactive protein, serum lipids and adipokines were measured. Subcutaneous abdominal adipose tissue biopsies were obtained to analyse the transcriptomics patterns of the isolated adipocytes as well as of the whole adipose tissue. Mitochondrial DNA transcript levels in adipocytes were measured by quantitative real-time PCR. Western blots of oxidative phosphorylation (OXPHOS) protein levels in adipocytes were performed in obese and lean unrelated individuals. The heavier (BMI 29.9 ± 1.0kg/m2) co-twins of the discordant twin pairs had more subcutaneous, intra-abdominal and liver fat and were more insulin resistant (p < 0.01 for all measures) than the lighter (24.1 ± 0.9kg/m2) co-twins. Altogether, 2538 genes in adipocytes and 2135 in adipose tissue were significantly differentially expressed (nominal p < 0.05) between the co-twins. Pathway analysis of these transcripts in both isolated adipocytes and adipose tissue revealed that the heavier co-twins displayed reduced expression of genes relating to mitochondrial pathways, a result that was replicated when analysing the pathways behind the most consistently downregulated genes in the heavier co-twins (in at least 12 out of 14 pairs). Consistently upregulated genes in adipocytes were related to inflammation. We confirmed that mitochondrial DNA transcript levels (12S RNA, 16S RNA, COX1, ND5, CYTB), expression of mitochondrial ribosomal protein transcripts and a major mitochondrial regulator PGC-1α (also known as PPARGC1A) were reduced in the heavier co-twins' adipocytes (p < 0.05). OXPHOS protein levels of complexes I and III in adipocytes were lower in obese than in lean individuals. Subcutaneous abdominal adipocytes in obesity show global expressional downregulation of oxidative pathways, mitochondrial transcripts and OXPHOS protein levels and upregulation of inflammatory pathways. The datasets analysed and generated during the current study are available in the figshare repository, https://dx.doi.org/10.6084/m9.figshare.3806286.v1.

Levels of Adipokines in Amniotic Fluid and Cord Blood Collected from Dichorionic-Diamniotic Twins Discordant for Fetal Growth.

ObjectiveTo compare the concentrations of adipokines in amniotic fluid (AF) and cord blood collected from discordant dichorionic-diamniotic (DCDA) twin fetuses.Study DesignThe study population included DCDA twins discordant for fetal growth (birth weight difference >10%) who either underwent mid-trimester amniocentesis for routine clinical indication (Cohort 1) or whose amniotic fluid was collected at the time of delivery (Cohort 2). In both cohorts, cord blood was collected at delivery.ResultsA total of 92 twin pairs were enrolled (n = 49 in Cohort 1; n = 43 in Cohort 2). In Cohort 1, the concentrations of adiponectin (median, 68.5 ng/mL vs 61.4 ng/mL; p<0.05) and leptin (median, 13.9 ng/mL vs 11.2 ng/mL; p<0.1) in mid-trimester AF were significantly higher in smaller compared with larger twins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; p<0.01) in AF at delivery was significantly higher in smaller twins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; p<0.005) and leptin (median, 2.1 ng/mL vs 2.6 ng/mL; p<0.005) were significantly lower in the cord blood of smaller twins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; p<0.05) was higher in the smaller twins.ConclusionIn discordant DCDA twin pairs, concentrations of adiponectin, leptin, and serpin E1 in mid-trimester AF, AF at delivery, and cord blood at birth vary significantly but predictably between the smaller and larger twins.