Twin Pairs Research Articles

Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors

Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior. Results Pre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p < 6.4*10–8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risks associated with CpGs were hypomethylated, and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body of NXN, rs480351) with increased risk for estrogen receptor positive BC and decreased risk for estrogen receptor negative BC. Conclusion While causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures.

Identification of risk factors for necrotizing enterocolitis in twins: a case-control matching analysis of over ten-years' experience.

The identification of risk factors is crucial for the clinical prevention and diagnosis of necrotizing enterocolitis (NEC). Monochorionic twins (MCT), due to the high genetic homogeneity, provided a valuable model for investigating the risk factors of various diseases. This study aimed to explore the risk factors for NEC using MCT. A retrospective review was conducted on the medical records of monochorionic twins (MCT) treated at Guangzhou Women and Children's Medical Center from January 2012 to March 2023. We compared perinatal condition, feeding and preceding condition between MCT pairs with NEC (NEC MCT) and without NEC(No NEC MCT).Logistic regression analysis was utilized to identify independent risk factors. In 85 pairs of monochorionic twins (MCT), NEC occurred in one twin in 78.8% of cases, whereas both twins were affected in 21.2% of cases. In the final cohort of 60 pairs of MCT, several parameters were found to differ significantly between NEC MCT group and No NEC MCT group. Compared to No NEC MCT group, the incidence of umbilical cord abnormalities was significantly higher in the NEC MCT group (25% vs. 8.3%, P = 0.014). Meanwhile, NEC MCT group showed higher prevalence of SGA infants (48.3% vs. 21.7%, P = 0.002) and sFGR (38.3% vs. 6.7%, P = 0.000). Furthermore, TTTs (13.3% vs. 3.3%, P = 0.027) and septicemia (25% vs. 5%, P = 0.002) were more common in NEC MCT group. In a multivariable logistic regression model, sFGR (OR 6.81,95%CI 2.1-21.9, p = 0.001) was eventually output as an independent risk factor. Non-genetic factors play a predominant role in the pathogenesis of NEC. Umbilical cord abnormalities, SGA, sFGR, TTTs and septicemia significantly increase the risk of NEC. sFGR is an independent risk factor of NEC.

Genetic and epigenetic factors affecting carotid intima-media thickness in monozygotic twins.

The intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins. We measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins. We identified a CpG site (cg02432467) on HS3ST6 as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with LINC01006 expression and IMT-Cmax. Furthermore, there were significant differences in AP2A2 expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism. We identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.

Determination of Twin Zygosity in Brazil: A DNA Validation of Two Short Questionnaires

Twin research in Brazil is expanding and should be built upon solid foundations using zygosity questionnaires validated through DNA. Our goals were to adapt and validate two short zygosity questionnaires to Brazilian Portuguese using DNA testing in Brazilian twins. One hundred same-sex twin pairs (27 males and 73 females; M age = 30.92, SD = 12.87) answered socio-demographic and two short zygosity questionnaires. Blood samples were collected for DNA extraction, followed by a forensic analysis on 22 autosomic short tandem repeat plus amelogenin and DYS391 markers to obtain an individual genetic profile. According to DNA tests, 17% of twin pairs were classified as dizygotic and 83% as monozygotic. Both questionnaires correctly distinguished the zygosity with 96.7% accuracy, with a high Kappa index, comparable with each original validation. These DNA validated zygosity questionnaires may foster twin research in Brazil with stronger methodology.

What is the ideal thyroid-stimulating hormone (TSH) threshold value in congenital hypothyroidism screening? Twin study.

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Therefore, the majority of developed countries have aimed to diagnose cases early through screening programs. In these screening programs, levels of thyroid-stimulating hormone (TSH) and free thyroxine are examined in dried blood spots taken between days 3 and 5 of life. While many countries accept TSH threshold value of 8 mU/L, there is still no consensus on the ideal TSH threshold value. As no twin studies on the TSH threshold value have been conducted previously, this study was planned. Eight pairs of twins were included in the study, with one of the twins having plasma TSH value ≥8 mU/L and the other <8 mU/L, measured between days 3 and 5 of life. The study aimed to investigate whether determining threshold TSH value of 8 mU/L would be beneficial by comparing somatic growth, mental development, and neuromotor development between twins. The age, gender, gestational weeks, birth weights, height, weight, and initial TSH values taken between days 3 and 5 of all cases were recorded. The patients' plasma Vitamin B12, folate, 25-OH Vitamin D, ferritin, and hemoglobin levels were measured. After that, they were evaluated by a child and adolescent psychiatry. Finally, the Denver Developmental Test was applied to the cases. There was no significant impairment in somatic growth, mental development, and neuromotor development in the long-term outcomes of cases with plasma TSH ≥ 8 mU/L compared to those with plasma TSH < 8 mU/L among the twins participating in our study.

From Globalization to Isolation: Exposure to the 2008 Financial Crisis and Three Dimensions of Liberal Attitudes in a Swedish Twin Design

Abstract This study investigates the link between non-liberal attitudes and adverse exposure to market disturbances during the 2008 global financial crisis, drawing from the premise that anti-liberal sentiments among Western voters stem from economic distress. We delve into three facets of liberal ideology in a Swedish sample: economic liberalism, liberal multiculturalism and liberal internationalism. Using variation in crisis exposure within identical twin pairs, comprehensive longitudinal economic data and detailed survey responses, we find no significant shift in economic or multicultural liberal attitudes with different crisis exposures. However, exposure to increased unemployment risk significantly lowered support for liberal internationalism, increasing scepticism towards global governance and multilateral cooperation.

Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study

BackgroundWe examined exposure to adulthood traumatic life events (TLEs) and their associations with depression in women and men. Then we examined whether those associations are independent of exposure loading and vulnerability including familial confounding. MethodsThe fourth survey in 2011 of the population-based Finnish Twin Cohort had 8410 participants (45 % men, mean age 60 years). Using the Center for Epidemiologic Studies Depression (CES-D) scale, depression was defined using a cut-off value ≥20. Participants reported exposure to TLEs during adulthood. Logistic regression adjusted for multiple covariates was used as the individual-based analyses. Familial confounding was tested using conditional logistic regression in 399 twin pairs discordant for depression. ResultsMore women (15 %) than men (11 %) were depressed. Men reported more traffic accidents (men: 11.8 %, women: 7.4 %), other serious accidents (11.8 %, 5.8 %), and violent crime (3.1 %, 2.0 %) whereas women reported more sexual assault (0.7 %, 10.6 %). Violent crime (Odds Ratio 3.86; 95 % Confidence Intervals 2.59, 5.73), sexual assault (3.49; 2.67, 4.55), physical assault (3.10; 2.45, 3.93), and other serious accidents (1.36; 1.01, 1.85) were associated with depression. These associations, except other serious accidents, remained significant after adjusting for multiple covariates including shared familial factors. The associations did not differ by sex. LimitationsA relatively small set of relevant TLEs was reported retrospectively and the order of TLEs was not assessed. ConclusionsWomen and men differ in exposure to TLEs but, if exposed, they are equally vulnerable for depression. Because traumatic life events are robustly associated with depression, they should be considered in treatment.

Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples.

Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation. To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions. We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs). Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins. These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Epigenetic Study of Cohort of Monozygotic Twins With Hypertrophic Cardiomyopathy Due to MYBPC3 (Cardiac Myosin-Binding Protein C).

Hypertrophic cardiomyopathy is an autosomal dominant cardiac disease. The mechanisms that determine its variable expressivity are poorly understood. Epigenetics could play a crucial role in bridging the gap between genotype and phenotype by orchestrating the interplay between the environment and the genome regulation. In this study we aimed to establish a possible correlation between the peripheral blood DNA methylation patterns and left ventricular hypertrophy severity in patients with hypertrophic cardiomyopathy, evaluating the potential impact of lifestyle variables and providing a biological context to the observed changes. Methylation data were obtained from peripheral blood samples (Infinium MethylationEPIC BeadChip arrays). We employed multiple pair-matched models to extract genomic positions whose methylation correlates with the degree of left ventricular hypertrophy in 3 monozygotic twin pairs carrying the same founder pathogenic variant (MYBPC3 p.Gly263Ter). This model enables the isolation of the environmental influence, beyond age, on DNA methylation changes by removing the genetic background. Our results revealed a more anxious personality among more severely affected individuals. We identified 56 differentially methylated positions that exhibited moderate, proportional changes in methylation associated with left ventricular hypertrophy. These differentially methylated positions were enriched in regions regulated by repressor histone marks and tended to cluster at genes involved in left ventricular hypertrophy development, such as HOXA5, TRPC3, UCN3, or PLSCR2, suggesting that changes in peripheral blood may reflect myocardial alterations. We present a unique pair-matched model, based on 3 monozygotic twin pairs carrying the same founder pathogenic variant and different phenotypes. This study provides further evidence of the pivotal role of epigenetics in hypertrophic cardiomyopathy variable expressivity.

Symmetric, Bilateral Auricular Calcifications in Twins With Noonan Syndrome.

Noonan syndrome (NS) is a rare, genetic multisystem disorder often presenting with associated craniofacial abnormalities. The authors report an identical twin pair with classical features of NS including short stature, mild ptosis, hypertelorism, down-slanting palpebral fissures, low-set angulated ears, and giant cell tumors in the craniofacial skeleton. Interestingly, these patients also presented with bilateral, symmetric, dystrophic auricular calcifications. Genome sequencing revealed identical germline son of sevenless homolog 1 mutations and inversion of chromosome 2 (p11.2q13). Awareness of the association of auricular calcifications and NS may help guide clinical management for these patients, particularly if auricular procedures are indicated.

“You and me”: Parental perceptions on asymmetry in twins' development and their dominance relationship dynamics

AbstractObjectiveThis study investigated the role of nontypical development in the relative dominance in twins' relationships throughout childhood.BackgroundDominance dynamics, affecting siblings' well‐being, are different in twins than in singletons for whom age and development often dictate sibling hierarchy. These dynamics in twins, who share similar ages and developmental contexts, remain underexplored and demand further understanding.MethodA longitudinal study surveyed 1,547 mothers and 536 fathers of 322 monozygotic (sharing nearly 100% genes) and 1,199 dizygotic (sharing 50% genetic variance) twin pairs, aged 3 to 8–9. Both parents reported on the twins' relationships. Mothers reported whether either twin had a developmental condition.ResultsNo dominance difference was found in similar developmental conditions dyads, whether both twins had typical or nontypical development. However, in dyads where twins differed in the developmental condition, nontypically developing twins were less dominant than their typically developing cotwins. This dominance imbalance persisted throughout childhood, even if initial developmental issues were resolved.ConclusionFrom parents' perspectives, nontypical development does not, in itself, prevent children from demonstrating dominance behaviors in twinship, but it is more likely that the asymmetry in developmental conditions is associated with the relationship between the twins.Implications and RecommendationsAccording to parents' perceptions, twins with nontypical development might experience imbalances in their relationship throughout childhood when their co‐twin is a typically developing child. However, demonstrating dominance might be possible for them in other contexts. Understanding these dominance dynamics is vital for caregivers, informing tailored parenting strategies and interventions to support the well‐being of children.

Differential postnatal cardiovascular course of donor-recipient twins and associated pathophysiology-a cohort study.

Fetal echocardiography in twin to twin transfusion pregnancies treated with photocoagulation noted impaired cardiac function. Systematic information about cardiac structure or function and arterial distensibility after birth is not available. This study evaluated cardiovascular function and arterial dynamic properties in survivors of twin to twin transfusion syndrome. Eleven pairs of donor-recipient twins were compared with each other, and with 20 singletons of comparable gestational age. The twin cohort was born at 31.5±2 weeks gestational age; birthweights of donors-recipients were comparable (donors: 1358±421g vs recipients: 1617±460g, P=0.2). Significant inter-twin differences were noted for cardiac function parameters. Recipients had greater septal thickness (donors: 2.3±0.15 vs recipients: 2.7±0.36mm, P=0.01) and globularity (lower sphericity index [donors: 1.76±0.1 vs recipients: 1.62±0.12, P=0.009]). They also had lower cardiac function (tricuspid annular plane systolic excursion [donors: 4.6±0.5 vs recipients: 4.1±0.4mm, P=0.02) and right ventricular fractional area change [donors: 30±1 vs recipients: 27.7±1.3%, P=0.0001]). Comparing with singletons, differences were statistically more significant for recipients. Arterial distensibility however, was more affected in donors (higher arterial wall stiffness index [donors: 2.5±0.2 vs recipients: 2.2±0.2, P=0.008] and lower pulsatile diameter [donors: 51±5 vs recipients: 63±10 µm, P<0.0001). Comparing with singletons, the differences were statistically more significant for donors. Evaluation in the neonatal period noted that cardiac function and arterial distensibility is affected in TTTS twins. These cohorts will benefit from close postnatal follow up for resolution of cardiac and arterial impairments.

Impact of Genetic and Environmental Factors on Peripheral Refraction.

Investigate genetic and environmental influences on refractive errors in monozygotic (MZ) and dizygotic (DZ) twin pairs. We assessed foveal and peripheral refractions in 54 MZ and 46 DZ twins, capturing three scans across the retina. The study focused on spherical equivalent (M) at the fovea (MLOS) and changes in midperipheral (δMmid-periphery), and peripheral (δMperiphery) defocus, along with nasal-temporal asymmetry (root mean squared error [RMSEASY]) and image shell contour (RMSEAVG). Genetic and environmental contributions were analyzed using structural equation models. No significant differences were observed between MZ and DZ twins for the examined variables. Intraclass correlations (ICC) indicated an important difference in genetic influence between MLOS, with the MZ twin pairs showing a higher correlation (0.83) than DZ (0.69) pairs, and δMperiphery, because the ICC for the MZ doubled (0.87) that of the DZ (0.42) pairs. Heritability estimates from the ACE model confirmed the large difference on genetic factors' influence on the variance for MLOS (0.13) and δMperiphery (0.77) change in refractive error. RMSEASY and RMSEAVG metrics showed significant genetic impact, particularly pronounced in the peripheral measurements, revealing high genetic control. The study delineates a marked environmental impact on central refractive errors, whereas genetic factors had a more significant influence on peripheral refractive variance and retinal image traits. Findings of the ACE model highlight the intricate genetic and environmental interplay in refractive error development, with a notable genetic dominance in peripheral vision characteristics. This suggests potential genetic targets for interventions in myopia management and emphasizes the need for personalized approaches based on genetic predispositions. Understanding the impact of genetics and environment on peripheral refraction is essential for deepening our fundamental knowledge of myopia and guiding the development of advanced myopia control strategies.

Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI

Background/Objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome. However, the role of genetics on the effects of exercise on intestinal GU and microbiome is unclear. Methods: Twelve monozygotic twin pairs discordant for BMI (age 40.4 ± 4.5 years, BMI heavier 36.7 ± 6.0, leaner 29.1 ± 5.7, 8 female pairs) performed a six-month-long training intervention. Small intestine and colonic insulin-stimulated GU was studied using [18F]FDG-PET and microbiota from fecal samples with 16s rRNA. Results: Ten pairs completed the intervention. At baseline, heavier twins had lower small intestine and colonic GU (p &lt; 0.05). Response to exercise differed between twins (p = 0.05), with leaner twins increasing colonic GU. Alpha and beta diversity did not differ at baseline. During the intervention, beta diversity changed significantly, most prominently at the mid-point (p &lt; 0.01). Beta diversity changes were only significant in the leaner twins when the twin groups were analyzed separately. Exercise was associated with changes at the phylum level, mainly at the mid-point (pFDR &lt; 0.05); at the genus level, several microbes increased, such as Lactobacillus and Sellimonas (pFDR &lt; 0.05). In type 1 analyses, many genera changes were associated with exercise, and fewer, such as Lactobacillus, were also associated with dietary sugar consumption (p &lt; 0.05). Conclusions: Obesity impairs insulin-stimulated intestinal GU independent of genetics. Though both twin groups exhibited some microbiota changes, most changes in insulin-stimulated colon GU and microbiota were significant in the leaner twins.

Aberrant Fetal Brain Sulcus Formation: A Clue to the Diagnosis of Sotos Syndrome.

This study aims to elucidate two distinct fetal ultrasound features associated with aberrant brain sulcus formation as potential prenatal markers for Sotos syndrome caused by mutations in the NSD1 gene. This retrospective study investigated three fetuses across two pregnancies, including a pair of monochorionic diamniotic twins, all diagnosed with Sotos syndrome via whole exome sequencing (WES). Comprehensive clinical and laboratory data were collected and analyzed. Each fetus underwent a series of specialized neurosonographic assessments to evaluate the development of the cerebral cortex. All three fetuses exhibited aberrant brain sulcus formation characterized by Sylvian fissure (SF) abnormalities and shallow parietooccipital sulcus (POS). WES revealed the presence of two de novo NSD1 variants in these fetuses. Fetal aberrant brain sulcus formation may represent a distinctive ultrasound feature indicative of Sotos syndrome, thereby offering additional diagnostic insights for the identification of this condition.

Predictive Indicators and Outcomes of Pregnancies Affected by Stage I Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Photocoagulation.

The significance of fetoscopic laser photocoagulation (FLP) in stage I twin-twin transfusion syndrome (TTTS) remains controversial. This study aimed to clarify the outcomes and prognostic factors of stage I TTTS after FLP. We conducted a retrospective cohort study on patients with stage I TTTS who underwent FLP in Japan. The primary outcome was neonatal survival at 28days. The adjusted odds ratios (aOR) of pre- and intraoperative factors for mortality in recipient and donor twins were calculated. This study included 272 twin pairs. The survival rate of at least one twin and both twins was 98% (267 pairs) and 85% (232 pairs), respectively. Survival of the recipient twin was observed in 253 cases (93%). No factor was associated with the mortality of the recipients. Among the donor twins, 246 (90%) survived. Preoperative twin anemia-polycythemia sequence (aOR, 17.45; 95% CI, 3.16-96.31) and arterio-arterial vascular anastomosis (AAA) identified at FLP (aOR, 2.78; 95% CI, 1.10-7.06) were independently associated with mortality of the donors. The neonatal survival rate for both recipient and donor twins was >90% among patients with stage I TTTS who underwent FLP. AAA is a risk factor for mortality in donors following FLP, though the pathophysiology of AAA remains to be clarified.

Multiomics integration unravels genotype‐microbiome interactions shaping the conjunctival transcriptome

AbstractGene expression is a molecular phenotype shaped by the interplay between genotype and environment. The microbiome represents a critical environmental exposure for the host. However, the genotype‐microbiome interactions (GMIs) shaping the host transcriptome remain largely unexplored. Here, we integrated conjunctival multiomics data from 120 pairs of twins to investigate GMIs. We identified 272,972 expression quantitative trait loci associated with 5946 genes and 241,073 genotype‐controlled correlations between gene expression and microbial abundance. We developed a modeling approach, MicroGenix, that screens for GMIs from host genome, transcriptome, and microbiome data and identifies GMIs associated with the disease through gene‐based association tests. We applied MicroGenix to the conjunctival data set and found that incorporating GMIs into gene expression prediction models significantly increased prediction accuracy. The genes with increased accuracy were overrepresented by those encoding cell adhesion molecules. We further used MicroGenix to predict the transcriptome from conjunctival metagenomes and identified GMIs associated with ocular surface disease. Our work provides a resource for studying host‐microbiome interactions at the conjunctiva and a computational approach to investigate GMIs using multiomics data.

Association between gut microbiota and diabetic nephropathy: a two-sample mendelian randomization study

BackgroundObservational studies have demonstrated the alterations of gut microbiota composition in diabetic nephropathy (DN), however, the correlation between gut microbiota and DN remains unclear.MethodsA two-sample Mendelian randomization (MR) analysis was designed to estimate the association between gut microbiota and DN. The summary statistics of gut microbiota from phylum level to genus level were obtained from a large-scale, genome-wide association study involving 18,340 individuals, and the data at the species level was derived from the study of TwinsUK Registry, including 1126 twin pairs. The summary statistics of DN were originated from the latest release data of FinnGen (R7, 299623 participants). The MR estimation was calculated using inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was assessed using Cochrane’s Q test.ResultsInverse variance weighted results indicated that the order Bacteroidetes and its corresponding class and phylum [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.15–2.17], the family Verrucomicrobiaceae and its corresponding class and order (OR, 1.46; 95% CI, 1.14–1.87), the genera Akkermansia (OR, 1.46; 95% CI, 1.14–1.87) and Catenibacterium (OR, 1.33; 95% CI, 1.07–1.66) might be associated with a higher risk of DN; whereas the genera Coprococcus2 (OR, 0.68; 95% CI, 0.51–0.91) and Eubacterium_coprostanoligenes_group (OR, 0.69; 95% CI, 0.52–0.92) might play protective roles in DN.ConclusionsThis MR study suggested that several gut bacteria were potentially associated with DN, further studies are required to validate these findings.

Genetic contribution to sleep homeostasis in early adolescence.

The sleep homeostatic process in adults is moderately stable over time and unique to an individual. Work in transgenic mice has suggested a role of genes in sleep homeostasis. The current study quantified the genetic contribution to sleep homeostasis in adolescence. We use slow wave energy (SWE) as a metric for sleep pressure dissipation during sleep. This measure reflects both sleep intensity and duration. High-density (58 derivations) sleep electroencephalogram (EEG) was recorded in 14 monozygotic and 12 dizygotic adolescent twin pairs (mean age = 13.2 years; standard deviation [SD] = 1.1; 20 females). SWE at the end of sleep was quantified as the cumulative delta power (1-4.6Hz) over the night. We also examined the time constant of the decay and the level of slow wave activity (SWA) at the beginning of the sleep episode. Structural equation modelling was used to quantify the amount of variance in SWE and the dissipation of sleep pressure due to genes. We found that most (mean = 76% across EEG derivations) of the variance in SWE was due to genes. In contrast, genes had a small (mean = 33%) influence on the rate of dissipation of sleep pressure, and this measure was largely (mean = 67%) driven by environmental factors unique to each twin. Our results show that the amount of dissipated sleep pressure is largely under genetic control; however, the rate of sleep pressure dissipation is largely due to unique environmental factors. Our findings are in line with research in animals and suggest that the heritability of the rate of sleep pressure dissipation is limited.

The interplay of genetic and environmental factors on the morphology of the limbic cortex and hippocampal subfields: Insights from an MRI twin study

IntroductionThe limbic system and the hippocampus are complex brain structures with key roles in memory, emotions, sexual stimulation and learning, with subregion abnormalities associated with a range of disorders and psychopathologies. Our study aimed to explore the heritability of specific subfield structures within the limbic system and hippocampus first in a Caucasian twin sample with volBrain pipeline. Materials and Methods59 healthy adult Caucasian twin pairs from the Hungarian Twin Registry without any history of previous neurodegenerative or cerebrovascular diseases underwent brain MRI on a 3.0 T scanner (43 monozygotic, MZ and 16 dizygotic, DZ pairs, with a median age of 50±+27 years). The volBrain automated volumetry pipeline was used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Based on age- and sex-adjusted MZ and DZ intra-pair correlations, the univariate ACE model was applied to calculate additive genetic, shared and unshared environmental influences. ResultsAdjusting for age and sex, moderate to strong heritability (A: 59.7 to 73.1 %) was found for most limbic cortex volumes, except for the volumes of entorhinal area and posterior cingulate gyrus where common environmental contribution was detected (C: 56.6 % and 65.0 %, respectively). A substantial heritability (A: 67.0 to 79.4 %) was estimated for the overall hippocampus and most subfield volumes, except for the CA2-CA3 region which was determinated by common environmental factors (C: 45.7 %). Unique environmental variance was a minor to moderate contributor across all variables (E: 20.6 to 54.3 %). ConclusionsAlbeit most limbic cortex, overall hippocampus and most subfield volumes are under substantial genetic influence in healthy adult twins, the volumes of entorhinal area, posterior cingulate gyrus and the CA2-CA3 region of the hippocampus are influenced common environmental factors. The findings underline the importance of unique environmental factors which may play a role in the prevention of disorders related to limbic cortex and hippocampus.