Discordant Twins Research Articles

A STUDY TO EVALUATE THE CLINICAL PROFILE OF MULTIPLE GESTATIONS: A HOSPITAL BASED SURVEY

Background: Monochorionic twins showed increased incidence of discordant growth as compared to dichorionic twins. Studies have reported fivefold mortality of twins in comparison with singleton pregnancy. In this a prospective study is done to assess the perinatal, neonatal mortality and morbidity in multiple gestations. Zygosity determines the degree of risk of chromosomal abnormalities in each fetus of a multiple gestation. The risk for aneuploidy in each fetus of an MZ pregnancy is the same as a singleton pregnancy, and except for rare cases of genetic discordancy, both fetuses are affected. In a DZ pregnancy, each twin has an independent risk for aneuploidy, and therefore has twice the risk of having a chromosomal abnormality compared with a singleton.
 Material and methods: This prospective observational study was conducted in the Department of Paediatrics Darbhanga Medical College and Hospital, Darbhanga Bihar India. The time period of the study from May 2019 to feb 2020. The total number of multiple gestation 160 include in this study.
 Results: Total 160 twins were studied, out of which preterm deliveries constituted 80.6% of all deliveries. Most of the mothers were between 24 to 30 year age group 70(43.8 %) followed by 18 to 24 year 55 (34.4 %) and most of them were primi 97(60.6%) and followed by gravid 2 was 54 (33.8%). Out of 160 patients 29 patient s was family history of twining in 18.1% of the study group. Assisted reproductive techniques such as clomiphene cirate,IUI and IVF were used by 19.4% of couples. Dichorinic diamniotic twins accounted for 84.4% and Dichorinic triamniotic 2.4 % of the total multiple deliveries. Normal Vaginal delivery was done for 65.6% of twins and LSCS for 34.4%.
 Conclusion: Most common type of delivery was vaginal delivery (65.6%) followed by LSCS (34.4%).Out of the variables studied, significant influence on neonatal mortality was seen only with discordant twins

Is the association between childhood maltreatment and aggressive behavior mediated by hostile attribution bias in women? A discordant twin and sibling study.

Understanding the mechanisms behind aggressive behavior (AGG) is vital so that effective prevention and intervention strategies can be developed. Maltreated children are hypothesized to be prone to social information processing biases, such as hostile attribution bias (HAB), which, in turn, may increase the likelihood of behaving aggressively. The first aim of the present study was to replicate findings regarding associations between childhood maltreatment (CM), HAB, and aggression in a population‐based sample of Finnish female twins and their sisters (N = 2,167). However, these associations might not be causal but instead confounded by familial factors, shared between the variables. The second aim was, thus, to test the associations when potential confounding by familial (genetic or common environmental) effects were controlled for using a multilevel discordant twin and sibling design within (a) 379 pairs of twins (n pairs = 239) or siblings (n pairs = 140), and (b) within the 131 monozygotic (MZ) twin pairs. Consistent with previous studies, HAB mediated the association between CM and AGG when familial confounding was uncontrolled. No support was found for the mediation when controlling for familial confounding. Between‐pair associations were found between CM and AGG, and between CM and HAB. In addition, within‐pair associations were found between HAB and AGG, and between CM and AGG, however, these were nonsignificant in the discordant MZ analysis, offering the most stringent control of familial confounding. The results indicate the necessity of taking familial confounding into account when investigating the development of AGG.

MiRNA expression profile changes in the peripheral blood of monozygotic discordant twins for epithelial ovarian carcinoma: potential new biomarkers for early diagnosis and prognosis of ovarian carcinoma

BackgroundOvarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs.MethodsThe study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.ResultsAfter the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.ConclusionsThe detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data.There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins.

Zika virus (ZIKV) causes congenital Zika syndrome (CZS), which is characterized by fetal demise, microcephaly and other abnormalities. ZIKV in the pregnant woman circulation must cross the placental barrier that includes fetal endothelial cells and trophoblasts, in order to reach the fetus. CZS occurs in ~1–40% of cases of pregnant women infected by ZIKV, suggesting that mothers’ infection by ZIKV during pregnancy is not deterministic for CZS phenotype in the fetus. Therefore, other susceptibility factors might be involved, including the host genetic background. We have previously shown that in three pairs of dizygotic twins discordant for CZS, neural progenitor cells (NPCs) from the CZS-affected twins presented differential in vitro ZIKV susceptibility compared with NPCs from the non-affected. Here, we analyzed human-induced-pluripotent-stem-cell-derived (hiPSC-derived) trophoblasts from these twins and compared by RNA-Seq the trophoblasts from CZS-affected and non-affected twins. Following in vitro exposure to a Brazilian ZIKV strain (ZIKVBR), trophoblasts from CZS-affected twins were significantly more susceptible to ZIKVBR infection when compared with trophoblasts from the non-affected. Transcriptome profiling revealed no differences in gene expression levels of ZIKV candidate attachment factors, IFN receptors and IFN in the trophoblasts, either before or after ZIKVBR infection. Most importantly, ZIKVBR infection caused, only in the trophoblasts from CZS-affected twins, the downregulation of genes related to extracellular matrix organization and to leukocyte activation, which are important for trophoblast adhesion and immune response activation. In addition, only trophoblasts from non-affected twins secreted significantly increased amounts of chemokines RANTES/CCL5 and IP10 after infection with ZIKVBR. Overall, our results showed that trophoblasts from non-affected twins have the ability to more efficiently activate genes that are known to play important roles in cell adhesion and in triggering the immune response to ZIKV infection in the placenta, and this may contribute to predict protection from ZIKV dissemination into fetuses’ tissues.

Childhood maltreatment and disordered gambling in adulthood: disentangling causal and familial influences.

Despite abundant research on the potential causal influence of childhood maltreatment (CM) on psychological maladaptation in adulthood, almost none has implemented the discordant twin design as a means of examining the role of such experiences in later disordered gambling (DG) while accounting for genetic and family environmental confounds. The present study implemented such an approach to disentangle the potential causal and familial factors that may account for the association between CM and DG. Participants were 3750 twins from the Australian Twin Registry [Mage = 37.60 (s.d. = 2.31); 58% female]. CM and DG were assessed separately via two semi-structured telephone interviews. Random-intercept generalized linear mixed models were fit to the data; zygosity, sex, educational attainment, childhood psychiatric disorder, adult antisocial behavior, and alcohol use disorder (AUD) were included as covariates. Neither quasi-causal nor familial effects of CM predicted DG after adjusting for covariates. Educational attainment appeared to reduce the risk of DG while AUD appeared to increase risk; evidence also emerged for familial effects of antisocial behavior on DG. Post-hoc analyses revealed a familial effect of CM on antisocial behavior, indicating that the association between CM and DG identified in unadjusted models and in prior studies may be accounted for by genetic and shared family environmental effects of antisociality. These findings add to the meager literature showing that CM does not exert a causal effect on DG, and present novel evidence that familial effects of antisocial behavior may account for the association between CM and DG identified in extant non-twin research.

First-Trimester Crown-Rump Length (CRL) and Nuchal Translucency (NT) Discordance in Monochorionic Twins: An Ominous Sign or a Benign Feature?

This study aimed to evaluate the usefulness of the first-trimester crown-rump length (CRL) and nuchal translucency (NT) discordance in monochorionic diamniotic twins (MCDA) for the prediction of complications-twin-twin transfusion syndrome (TTTS), selective fetal growth restriction (sFGR) or intrauterine fetal demise (IUFD). Intertwin discordance in the CRL and NT was calculated as a percentage of the larger CRL and NT, respectively. The performance of inter twin discordance (CRL ≥ 10% and NT≥ 20%) for predicting complications was analysed using standard statistical screening test methods. Fifty-eight MCDA twin pregnancies were studied. Out of them, 19 (32%) pregnancies resulted in one of the complications studied (4 TTTS, 10 sFGR, 5 IUFD). CRL and NT discordance showed an increased probability of developing complications positive likelihood ratio (LR+) {95% confidence interval}: 2.05 {0.46-9.23} and 1.88 {1.03-3.45}, respectively. NT discordance showed a sensitivity of 57%. Although discordant first-trimester CRL and NT in monochorionic twins are poor screening tools for early prediction, if positive, they increase the risk of developing complications.

Predictive value of prenatal ultrasound parameters for dichorionic growth discordant twins

BackgroundTwin growth discordance was demonstrated to be a risk factor for adverse perinatal outcomes, and prenatal ultrasonographic methods were utilized to predict twin growth discordance to improve outcomes. The results currently reported are not consistent due to the poor unified parameters and gestational durations.MethodsA total of 71 dichorionic twins with growth discordance and 346 dichorionic twins with normal growth were respectively included in the retrospective cohort study. The weight discordance of more than 25% was defined as a “growth discordant twin”. The clinical baseline information, maternal outcomes, twin birth weights and fetal growth parameters (which were measured by ultrasound) were compared between the two groups from early gestation to late gestation. Multiple logistic regression and receiver operating characteristic curves were adopted to evaluate the predictive value of the growth parameters.ResultsCompared with normal dichorionic twins, the clinical baseline conditions were similar in the twins those finally developed growth discordance. The fetal growth parameters and the deepest volume pocket of amniotic fluid in early and mid-pregnancy showed no obvious predictive values. The fetal growth parameters in late pregnancy showed predictive values, especially the discordance of estimated fetal weight (EFW) in the early third-trimester (P < 0.001, area under the curve, 0.822; the cut-off value, 20%; sensitivity, 66.67%; specificity, 91.30%; positive predictive value, 88.46%).ConclusionTwo assessment approaches were suggested and adopted to predict twin growth discordance in the current study. Twin growth should be assessed longitudinally and dynamically. Normal twins may show growth imbalance in the early stage. The discordance of EFW in late pregnancy may be a useful indicator for a growth discordance of more than 25%, which is required further confirmation.

Critical Coarctation of the Aorta in Selective Fetal Growth Restriction and the Role of Coronary Stent Implantation

Introduction: Monochorionic twins are at increased risk of congenital heart defects (CHDs). Up to 26% have a birth weight <1,500 g, a CHD requiring neonatal surgery, therefore, poses particular challenges. Objective: The aim of the study was to describe pregnancy characteristics, perinatal management, and outcome of monochorionic twins diagnosed with critical coarctation of the aorta (CoA). Methods: We included monochorionic twins diagnosed with critical CoA (2010–2019) at 2 tertiary referral centers, and we systematically reviewed the literature regarding CoA in monochorionic twins. Results: Seven neonates were included. All were the smaller twin of pregnancies complicated by selective fetal growth restriction. The median gestational age at birth was 32 weeks (28–34). Birth weight of affected twins ranged as 670–1,800 g. One neonate underwent coarctectomy at the age of 1 month (2,330 g). Six underwent stent implantation, performed between day 8 and 40, followed by definitive coarctectomy between 4 and 9 months in 4. All 7 developed normally, except for 1 child with neurodevelopmental delay. Three co-twins had pulmonary stenosis, of whom 1 required balloon valvuloplasty. The literature review revealed 10 cases of CoA, all in the smaller twin. Six cases detected in the first weeks after birth were treated with prostaglandins alone, by repeated transcatheter angioplasty or by surgical repair, with good outcome in 2 out of 6. Conclusions: CoA specifically affects the smaller twin of growth discordant monochorionic twin pairs. Stent implantation is a feasible bridging therapy to surgery in these low birth weight neonates.

Influence of Prenatal Environment on Androgen Steroid Metabolism In Monozygotic Twins With Birthweight Differences

Although low birthweight (bw) and unfavorable intrauterine conditions have been associated with metabolic sequelae in later life, little is known about their impact on steroid metabolism. We studied genetically identical twins with intra-twin bw-differences from birth to adolescence to analyze the long-term impact of bw on steroid metabolism. 68 monozygotic twin pairs with a bw-difference of <1 standard deviation score (SDS; concordant; n = 41) and ≥1 SDS (discordant; n = 27) were recruited. At 14.9 years (mean age), morning urine samples were collected and analyzed with gas chromatography-mass-spectrometry. No significant differences were detected in the concordant group. In contrast, in the smaller twins of the discordant group, we found significantly higher concentrations not only of the dehydroepiandrosterone sulfate (DHEAS) metabolite 16α-OH-DHEA (P = 0.001, 656.11 vs 465.82 µg/g creatinine) but also of cumulative dehydroepiandrosterone and downstream metabolites (P = 0.001, 1650.22 vs 1131.92 µg/g creatinine). Relative adrenal (P = 0.002, 0.25 vs 0.18) and overall androgen production (P = 0.001, 0.79 vs 0.65) were significantly higher in the formerly smaller discordant twins. All twin pairs exhibited significant intra-twin correlations for all individual steroid metabolites, sums of metabolites, indicators of androgen production, and enzyme activities. Multiple regression analyses of the smaller twins showed that individual steroid concentrations of the larger co-twin were the strongest influencing factor among nearly all parameters analyzed. In monozygotic twin pairs with greater intra-twin bw-differences (≥1 SDS), we found that bw had a long-lasting impact on steroid metabolism, with significant differences regarding DHEAS metabolites and relative androgen production. However, most parameters showed significant intra-twin correlations, suggesting a consistent interrelationship between prenatal environment, genetic background, and steroid metabolism.

Metabolic Profile and Body Composition in Twins Concordant and Discordant for Physical Exercise.

The aim of this study was to evaluate the differences in the metabolic profile and body composition of monozygotic (MZ) twins concordant and discordant for the practice of physical exercise. The sample consisted of 92 MZ twins (72.5% female and 27.5% male, mean age 25.4 ± 5.69 years), registered with the Brazilian Registry of Twins, residing in Natal, Brazil. Data collection was carried out between the years 2016 and 2018. On day 1, subjects underwent a whole-body fitness evaluation, including measures of weight, height, body composition by Dual-Energy X-ray Absorptiometry and the Cardiorespiratory Exercise Test. On day 2, 10 ml blood samples were collected (overnight fasting) to determine the lipid profile and fasting glucose. The sample was separated into three groups: Active Concordant twins (Concordant A, n = 44 subjects), Inactive Concordant twins (Concordant I, n = 22 subjects) and Discordant pairs for Physical Exercise (Discordant PE, n = 26 subjects). The results demonstrated a difference between the discordant twins for exercise and also between the active versus sedentary groups, indicating a causal effect of exercise on the fat percentage, maximum oxygen consumption (VO2max) and second ventilatory threshold variables. Between groups, a difference was also observed between the groups in ventilatory threshold, very low-density lipoprotein and triglycerides. We concluded that, regardless of genetics, the practice of physical exercise was sufficient to generate alterations in body composition and VO2max in MZ twins, but not in the lipid profile or fasting glucose.

The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases.

Genomic predisposition cannot explain the onset of complex diseases, as well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodelling and non-coding RNA, are considered to be the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. The paradigmatic cases of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's syndrome (SjS) and type-1 diabetes (T1D) share the loss of immunological tolerance to self-antigen influenced by several factors, with a largely incomplete role of individual genomic susceptibility. The most widely investigated epigenetic mechanism is DNA methylation which is associated with gene silencing and is due to the binding of methyl-CpG binding domain (MBD)-containing proteins, such as MECP2, to 5-methylcytosine (5mC). Indeed, a causal relationship occurs between DNA methylation and transcription factors occupancy and recruitment at specific genomic locus. In most cases, the results obtained in different studies are controversial in terms of DNA methylation comparison while fascinating evidence comes from the comparison of the epigenome in clinically discordant monozygotic twins. In this manuscript, we will review the mechanisms of epigenetics and DNA methylation changes in specific immune-mediated rheumatic diseases to highlight remaining unmet needs and to identify possible shared mechanisms beyond different tissue involvements with common therapeutic opportunities. Key Points • DNA methylation has a crucial role in regulating and tuning the immune system. • Evidences suggest that dysregulation of DNA methylation is pivotal in the context of immune-mediated rheumatic diseases. • DNA methylation dysregulation in FOXP3 and interferons-related genes is shared within several autoimmune diseases. • DNA methylation is an attractive marker for diagnosis and therapy.

Education and voter turnout revisited: Evidence from a Swedish twin sample with validated turnout data

The association between education and voter turnout is well-established in almost a century of research. The causal status of this correlation, however, is still subject to debate. Results in the previous literature differ substantially, and this may reflect both methodological differences and heterogeneous effects across populations or types of elections. This study addresses the question using a discordant twin design and variance decomposition methods with validated turnout data for both first- and second-order elections in a large sample of Swedish twins, paired with population-wide sibling data. Results show that education does not have an effect on national electoral turnout, but does have an effect on turnout in the European elections. Furthermore, the association between education and turnout is shown to be affected by substantial genetic confounding, which leaves a non-trivial amount of bias even in sibling based designs. This underscores the importance of taking genetic confounding seriously in observational research.

An Approach to Biomarker Discovery of Cannabis Use Utilizing Proteomic, Metabolomic, and Lipidomic Analyses.

Introduction: Relatively little is known about the molecular pathways influenced by cannabis use in humans. We used a multi-omics approach to examine protein, metabolomic, and lipid markers in plasma differentiating between cannabis users and nonusers to understand markers associated with cannabis use. Methods: Eight discordant twin pairs and four concordant twin pairs for cannabis use completed a blood draw, urine and plasma toxicology testing, and provided information about their past 30-day cannabis use and other substance use patterns. The 24 twins were all non-Hispanic whites. Sixty-six percent were female. Median age was 30 years. Fifteen participants reported that they had used cannabis in the last 30 days, including eight participants that used every day or almost every day (29-30 of 30 days). Of these 15 participants, plasma 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and total tetrahydrocannabinol (THC) concentrations were detectable in 12 participants. Among the eight "heavy users" the amount of total THC (sum of THC and its metabolites) and plasma THC-COOH concentrations varied widely, with ranges of 13.1-1713 ng/mL and 2.7-284 ng/mL, respectively. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay measured plasma THC-COOH, THC, and other cannabinoids and metabolites. Plasma THC-COOH was used as the primary measure. Expression levels of 1305 proteins were measured using SOMAScan assay, and 34 lipid mediators and 314 metabolites were measured with LC-MS/MS. Analyses examined associations between markers and THC-COOH levels with and without taking genetic relatedness into account. Results: Thirteen proteins, three metabolites, and two lipids were identified as associated with THC-COOH levels. Myc proto-oncogene was identified as associated with THC-COOH levels in both molecular insight and potential marker analyses. Five pathways (interleukin-6 production, T lymphocyte regulation, apoptosis, kinase signaling pathways, and nuclear factor kappa-light-chain-enhancer of activated B cells) were linked with molecules identified in these analyses. Conclusions: THC-COOH levels are associated with immune system-related pathways. This study presents a feasible approach to identify additional molecular markers associated with THC-COOH levels.

IGF-I in cord blood is predictive of final height in monozygotic twins with intra-twin birth weight differences.

Adverse prenatal conditions can exert a long-lasting impact on growth up to final height (FH). Due to different prenatal nutrient availability, monozygotic twin pairs with discordant birth weight (bw) provide an excellent model to examine the impact of genes and environment and to analyse the predictive value of bw, birth length (bl) and cord blood (cb) concentration of IGF-I on FH. Twenty eight monozygotic twin pairs with intra-twin bw-/bl-differences were studied at birth and longitudinally until FH. Intra-twin bw difference >1 SDS was defined "discordant" (n=10 pairs). IGF-I was analysed in cord blood in all twins. Intra-twin differences (∆) in bw, bl and cord blood IGF-I were correlated with ∆FH. Throughout growth and up until FH intra-twin length/height differences remained for all but two (26/28) twins and for all (10/10) discordant twins. In the discordant group, a highly significant intra-twin difference for FH-SDS was found with a mean intra-twin Δheight- SDS of 1.23 (range, 0.29-2.34). This corresponds to a mean Δintra-twin difference at FH of 7.9cm (3.1 inch; range, 2-15cm [0.79-5.9 inch]). Correlation coefficients were calculated to identify factors predicting FH: ∆bw (r=.678; P=.0005), ∆bl (r=.333; P=.0002) and ∆IGF-I in cb (r=.418; P=.0023). Interaction terms showed that IGF-I is an additional factor to the auxological data, leading to an improvement of the ∆FH modelling. Prenatal environment leading to bw-/bl- and cbIGF-I differences in monozygotic twins had a long-lasting impact on growth until FH. Both, anthropometric data at birth and cbIGF-I are predictive of FH.

Illicit drug use and the genetic overlap with Cannabis use

BackgroundThe use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal association. MethodsPolygenic scores for lifetime cannabis use were generated in a sample of Dutch participants (N = 8348). We tested the association of a PGS for cannabis use with ecstasy, stimulants and a broad category of illicit drug use. To explore the nature of the relationship: (1) these analyses were repeated separately in cannabis users and non-users and (2) monozogytic twin pairs discordant for cannabis use were compared on their drug use. ResultsThe lifetime prevalence was 24.8 % for cannabis, 6.2 % for ecstasy, 6.5 % for stimulants and 7.1 % for any illicit drug use. Significant, positive associations were found between PGS for cannabis use with ecstasy use, stimulants and any illicit drug use. These associations seemed to be stronger in cannabis users compared to non-users for both ecstasy and stimulant use, but only in people born after 1968 and not significant after correction for multiple testing. The discordant twin pair analyses suggested that cannabis use could play a causal role in drug use. ConclusionsThe genetic liability underlying cannabis use significantly explained variability in ecstasy, stimulant and any illicit drug use. Further research should further explore the underlying mechanism to understand the nature of the association.

Joint impact of common risk factors on incident dementia: A cohort study of the Swedish Twin Registry.

As common risk factors of dementia, nine factors (low education, hearing loss, obesity, hypertension, smoking, depression, physical inactivity, diabetes and social isolation) were proposed. However, the joint impact of these factors on incident dementia is still uncertain; hence, we aimed to examine this impact. We conducted a cohort study of 9017 cognitively intact individuals aged≥65years in the Swedish Twin Registry. The main exposure was the total number of reported risk factors (ranging from 0 to 9). Data on dementia diagnoses were based on clinical workup and national health registers. After estimating the adjusted hazard ratios of incident dementia, the population attributable fraction (PAF) was calculated. We then conducted additional analyses, including APOE ε4 status in a genotyped subsample (n=2810) to check the relative impact of the main exposure and discordant twin pair (n=1158) analysis to consider confounding by familial effects (shared genetic or familial environmental factors). The number of dementia cases was 1950 (21.6%). A dose-response relationship between the number of risk factors and incident dementia was observed; hazard ratio (95% confidence interval) per one-unit increment in number of risk factors was 1.07 (1.03 to 1.11). The PAF for the combination of the nine risk factors was 10.4%. The PAF of all nine risk factors was smaller than that of APOE ε4 genotype (20.8%) in the subsample. Discordant pair analysis suggested that the observed association was notlikely explained by familial effects. The nine risk factors may have considerable impact as modifiable factors on incident dementia.

Gram-negative Microbiota Blooms in Premature Twins Discordant for Parenteral Nutrition-associated Cholestasis.

Parenteral nutrition-associated cholestasis (PNAC) causes serious morbidity in the neonatal intensive care unit. Infection with gut-associated bacteria is associated with cholestasis, but the role of intestinal microbiota in PNAC is poorly understood. We examined the composition of stool microbiota from premature twins discordant for PNAC as a strategy to reduce confounding from variables associated with both microbiota and cholestasis. Eighty-four serial stool samples were included from 4 twin sets discordant for PNAC. Random Forests was utilized to determine genera most discriminatory in classifying samples from infants with and without PNAC. In infants with PNAC, we detected a significant increase in the relative abundance of Klebsiella, Veillonella, Enterobacter, and Enterococcus (P < 0.05). Bray-Curtis dissimilarities in infants with PNAC were significantly different (P < 0.05) from infants without PNAC. Our findings warrant further exploration in larger cohorts and experimental models of PNAC to determine if a microbiota signature predicts PNAC, as a basis for future interventions to mitigate liver injury.

The black sheep of the family- whole-exome sequencing in family of lithium response discordant bipolar monozygotic twins

Twin studies are among the most promising strategies for studying heritable disorders, including bipolar disorder (BD).The aim of the present study was to identify distinguishing genes between monozygotic (MZ) twins with different BD phenotype and compare them to their non-affected siblings.Whole-exome sequencing (WES) can identify rare and structural variants that could detect the polygenetic burden of complex disorders. WES was performed on a family composed of two MZ twins with BD, their unaffected brother and unaffected parents. The twins have a discordant response to lithium and distinct course of illness. Following WES, six genes of particular interest emerged: Neurofibromin type 1 (NF1), Biorientation of chromosomes in cell division 1 (BOD1), Golgi-associated gamma adaptin ear-containing ARF binding protein 3 (GGA3), Disrupted in schizophrenia 1 (DISC1), Neuromedin U receptor 2 (NMUR2), and Huntingtin interacting protein 1-related (HIP1R). Interestingly, many of these influence glutamatergic pathways and thus the findings may have therapeutical implications. These results may provide important insights to unveil genetic underpinnings of BD and the response to lithium

The Effect of Twin Sex on Menstrual Characteristics.

Background and objectives: The purpose of this project is to evaluate the association between twin sex discordance and menstrual characteristics. We hypothesize that sharing the uterus with a male twin can change ovulation programming, hence changing the menstrual cycle characteristics during adulthood. This project could be novel in discovering new physiological mechanisms of hormone exposure and menstrual cycles. Materials and methods: This is a cross-sectional study. We asked females from sex-concordant (n = 1290) and sex-discordant (n = 168) twin pairs in the Washington State Twin Registry about characteristics of menstrual cycles. Generalized Estimating Equation (GEE) analysis was used to compare groups. The main outcome measures included the amount of bleeding, duration of menstruation, the timing of menstruation, length of menstruation, and a number of periods per year. Results: We found a statistically significant association between the amount of menstrual period bleeding and twin sex discordance (0.42 (95% CI 0.18–0.94)). However, twin sex discordance was not associated with period duration, length of menstrual cycle, cycle regularity, or a number of periods per year. Conclusions: Twin sex discordance is not a predictor of clinical characteristics of menstruation during adulthood except for the amount of bleeding. Future studies should focus on the impact of male hormones on the amount of bleeding during menstruation.

Impact of growth discordance in twins on preeclampsia based on chorionicity

Despite extensive investigations over the last decade, preeclampsia remains an unpredictable pregnancy complication causing perinatal morbidity and mortality worldwide, particularly in twin pregnancies. This study aimed to determine the relationship between growth discordance in twin pregnancies and the risk for preeclampsia based on chorionicity. This was a retrospective single-center study that included 2122 women with twin pregnancies who were admitted to a tertiary hospital between January 2013 and June 2016. Growth discordance was defined as twin birthweight difference ≥20%. Logistic regression models were used to analyze the association between growth discordance and risk for gestational hypertension-preeclampsia in all subjects. Stratified sampling by twin chorionicity (dichorionic and monochorionic) was also conducted. Further analysis was performed to estimate the association between the degree of growth discordance and gestational hypertension-preeclampsia risk in monochorionic and dichorionic twin pregnancies. The prevalence of growth discordance was 17.6%. In all subjects, growth discordance was associated with increased risk for gestational hypertension-preeclampsia. After stratification by twin chorionicity, growth discordance was associated with an increased risk for gestational hypertension preeclampsia (adjusted odds ratio [AOR], 1.84; 95% confidence interval [CI], 1.26-2.67) and preeclampsia (AOR, 1.82; 95% CI, 1.21-2.73), including mild preeclampsia (AOR, 1.86; 95% CI, 1.02-3.37), severe preeclampsia (AOR, 1.78; 95% CI, 1.06-2.97; P<.05), and early-onset preeclampsia (AOR, 2.98; 95% CI, 1.40-6.32), in the dichorionic twin pregnancy group; however, no significant association was found in the monochorionic twin pregnancy group. A 10% increment of growth discordance in the dichorionic twin pregnancy group was associated with an elevated risk for gestational hypertension preeclampsia (AOR, 1.20; 95% CI, 1.02-1.41) and preeclampsia (AOR, 1.24; 95% CI, 1.04-1.48), including severe preeclampsia (AOR, 1.28; 95% CI, 1.04-1.59) and early-onset preeclampsia (AOR, 1.47; 95% CI, 1.08-2.00), but no significant association was found in the monochorionic twin pregnancy group. Growth discordance is associated with an increased risk for preeclampsia in dichorionic but not in monochorionic twin pregnancy. In addition, the prevalence of preeclampsia increases significantly with increasing degree of growth discordance, reflecting a dose-response relationship in dichorionic twin pregnancy.