Monozygotic Twin Pairs Research Articles

Epigenome-wide association study of loneliness in a sample of U.S. middle-aged twins

ABSTRACT Loneliness is a complex human trait that is highly polygenic and found to affect gene expression related to inflammatory and immunological functioning. To date, no epigenome-wide association studies of loneliness have tested whether differentially methylated sites are annotated to genes associated with inflammatory and immunological processes. Using 281 individual adult twins’ DNA methylation data from the Louisville Twin Study, we performed an epigenome-wide analysis of loneliness to address this gap in the literature. In the discovery analysis, 169 twins were used to prioritize probes and test associations with DNA methylation age acceleration, and 56 independent monozygotic (MZ) twin pairs (112 individuals) were used in a within-family replication analysis. Among the 837,274 sites analyzed, no probe sites were statistically significant at the genome-wide level (p < 5.97 × 10−8), but 25 suggestive sites (p < 5 × 10−5) were annotated to genes related to various biological processes, including inflammatory response and protein-binding functions that extend prior findings. The nominal associations at these suggestive probe sites were highly correlated (r = .72) between the discovery sample and the MZ pair replication sample. Finally, loneliness significantly correlated with the DunedinPACE DNA methylation measure, suggesting that higher levels of loneliness were associated with accelerated epigenetic age as quantified by a measure that indexes longitudinal changes across multiple organ systems.

Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism

BackgroundA large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.MethodsBy applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.ResultsUsing gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D. Differential expression levels of one or more predicted target relevant miRNA(s) were identified for approximately 35% of the dysregulated GSEA pathways. These include miRNAs with a significant overrepresentation of targets involved in GLUT4 translocation (miR-4643 and miR-548z), signaling by receptor tyrosine kinases pathways (miR-607), and muscle contraction (miR-4658). Acquired DNA methylation changes in skeletal muscle were quantitatively small in twins with T2D compared with the co-twins without T2D. Key methylation and expression results were validated in muscle, myotubes, and/or myoblasts from unrelated subjects with T2D and controls. Finally, mimicking T2D-associated changes by overexpressing miR-548 and miR-607 in cultured myotubes decreased expression of target genes, GLUT4 and FGFR4, respectively, and impaired insulin-stimulated phosphorylation of Akt (Ser473) and TBC1D4.ConclusionsTogether, we show that T2D is associated with non- and epigenetically determined differential transcriptional regulation of pathways regulating skeletal muscle metabolism and contraction.

Similarities and differences in diurnal salivary adrenal hormones in monozygotic twins with discordant birthweight.

Introduction DHEAS is increased in formerly small-for-gestational-age singletons and in smaller twins compared to their normal-weight co-twin. Less is known concerning other adrenal hormones. We compared diurnal salivary profiles in monozygotic twins with intra-twin birthweight(bw)-differences to analyse the long-term impact of bw and persistent intra-twin auxological differences on various adrenal hormones. Methods 46 monozygotic pre-pubertal twin-pairs with bw-difference of <1SDS (concordant; n=29, 13 female) and ≥1SDS (discordant; n=17, 6 female) were recruited. At a mean age of 6.9 years (yrs) saliva samples were collected (7 am/waking, 1 pm, 6 pm, and 9 pm) and analysed with liquid chromatography-tandem mass spectrometry. Results Diurnal salivary concentrations showed significant intra-twin correlations in all twin-pairs for nearly all time-points: progesterone and androstenedione (4/4 time-points), 17-hydroxyprogesterone (2/4). However, in the discordant group mean progesterone differed significantly (p=0.018) between the smaller (3.27nmol/L, SD 3.87) and the larger twin (0.72nmol/L, SD 0.42) at 7 am and intra-twin differences were observed at 3/4 time-points. Regression analyses of intra-twin differences confirmed that actual hormonal parameters were explained mainly by the co-twin parameter. However, at 6 pm progesterone concentration of the smaller twin was explained by bw (Β -1.102; SE 0.563; p=0.05) and actual weight (Β 0.799; SE 0.327; p=0.019). Conclusion The significant correlations within monozygotic twin-pairs in all measured hormones at nearly all time-points suggest a strong genetic influence on the adrenal axis. Among the discordant twin pairs, we found significant variations in progesterone, suggesting additional long-lasting influence from intrauterine conditions on adrenal hormones with possible metabolic consequences. Word count 249.

Multi-omic analyses of a twin pair with mirror image cleft lip identifies pathogenic variant in FGF20 modified by differential methylation upstream of ZFP57.

Disturbances in the intricate processes that control craniofacial morphogenesis can result in birth defects, most common of which are orofacial clefts (OFCs). Nonsyndromic cleft lip (nsCL), one of the phenotypic forms amongst OFCs, has a non-random laterality presentation with the left side being affected twice as often compared to the right side. This study investigates the etiology of nsCL and the factors contributing to its laterality using a pair of monozygotic twins with mirror-image cleft lip. We conducted whole-genome sequencing (WGS) analyses in a female twin pair with mirror image nsCL, their affected mother and unaffected father to identify etiopathogenic variants. Additionally, to identify possible cleft lip laterality modifiers, DNA-methylome analysis was conducted to test for differential methylation patterns between the mirror twins. Lastly, DNA methylation patterns were also analyzed on an independent cohort of female cases with unilateral cleft lip (left=22; right=17) for replication purposes. We identified a protein-altering variant in FGF20 (p.Ile79Val) within the fibroblast growth factor interacting family domain segregating with the nsCL in this family. Concurrently, DNA-methylome analysis identified differential methylation regions (DMRs) upstream of Zinc-finger transcription factor ZFP57 (Δβ > 5%). Replication of these results on an independent cohort, confirmed these DMRs, emphasizing their biological significance (p<0.05). Enrichment analysis indicated that these DMRs are involved in DNA methylation during early embryo development (FDR adjusted p-value = 1.3241E-13). Further bioinformatics analyses showed one of these DMRs acting as a binding site for transcription factor AP2A ( TFAP2A ), a key player in craniofacial development. Interactome analysis also suggested a potential role for ZFP57 in left/right axis specification, thus emphasizing its significance in cleft laterality. This study provides novel insights into the etiology of nsCL and its laterality, suggesting an interplay between etiopathogenic variants and DNA methylation in cleft laterality. Our findings elucidate the intricate mechanisms underlying OFCs development. Understanding these factors may offer new tools for prevention and management of OFCs, alleviating the burden on affected individuals, their families and global health.

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

Background and aimsThe 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. MethodsWe 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. ResultsWe 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. ConclusionsWe identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.

A similar severe fibrosis pattern in a monozygotic twin pair with the TRIM63 variant manifesting as hypertrophic cardiomyopathy.

A similar severe fibrosis pattern in a monozygotic twin pair with the TRIM63 variant manifesting as hypertrophic cardiomyopathy.

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.

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.

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.

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. 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. Ten pairs completed the intervention. At baseline, heavier twins had lower small intestine and colonic GU (p < 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 < 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 < 0.05); at the genus level, several microbes increased, such as Lactobacillus and Sellimonas (pFDR < 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 < 0.05). 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.

Twin study identifies early immunological and metabolic dysregulation of CD8+ T cells in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8+ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8+ T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8+ T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8+ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.

The Neural Underpinnings of Aphantasia: A Case Study of Identical Twins.

Aphantasia is a condition characterized by reduced voluntary mental imagery. As this lack of mental imagery disrupts visual memory, understanding the nature of this condition can provide important insight into memory, perception, and imagery. Here, we leveraged the power of case studies to better characterize this condition by running a pair of identical twins, one with aphantasia and one without, through mental imagery tasks in an fMRI scanner. We identified objective, neural measures of aphantasia, finding less visual information in their memories which may be due to lower connectivity between frontoparietal and occipitotemporal lobes of the brain. However, despite this difference, we surprisingly found more visual information in the aphantasic twin's memory than anticipated, suggesting that aphantasia is a spectrum rather than a discrete condition.

Functional landscape of genome-wide postzygotic somatic mutations between monozygotic twins.

Monozygotic (MZ) twins originate from a single fertilized egg, making them genetically identical at the time of conception. However, postzygotic somatic mutations (PZMs) can introduce genetic differences after separation. Although whole-genome sequencing (WGS) sheds light on somatic mutations in cancer genomics, its application in genomic studies of MZ twins remains limited. In this study, we investigate PZMs in 30 healthy MZ twin pairs from the Osaka University Center for Twin Research using WGS (average depth = 23.8) and a robust germline-calling algorithm. We find high genotype concordance rates (exceeding 99%) in MZ twins. We observe an enrichment of PZMs with variant allele frequency around 0.5 in twins with highly concordant genotypes. These PZMs accumulate more frequently in non-coding regions compared with protein-coding regions, which could potentially influence gene expression. No significant association is observed between the number of PZMs and age or sex. Direct sequencing confirms a missense mutation in the ANKRD35 gene among the PZMs. By applying a genome-wide mutational signature pattern technique, we detect an age-related clock-like signature in these early postzygotic somatic mutations in MZ twins. Our study provides insights that contribute to a deeper understanding of genetic variation in MZ twins.

Two identical twin pairs discordant for longstanding anorexia nervosa and OSFED: lived experience accounts of eating disorder and recovery processes

Research into the risk of anorexia nervosa (AN) has examined twin pairs to further the understanding of the contributions of genetics, trait inheritance, and environmental factors to eating disorder (ED) development. Investigations of twin experiences of EDs have been biologically-based and have not considered the qualitative, phenomenological aspects of twin experiences. A gap in the literature exists regarding understanding of discordant twins with EDs. This research was developed in response, with the aim to deepen understanding of AN in discordant twins and to create novel ideas for further research and testing. The case studies presented in this article provide lived experience insights of two identical discordant twin pairs: one twin pair discordant for longstanding AN and one twin pair discordant for ‘atypical’ AN (the twin with AN has recovered). The perspectives and experiences of each co-twin (one with AN and one without) explore a number of factors that may have contributed to twin discordance in these cases, and how each twin has responded to the impact of AN in their lives. Through use of first-person accounts in case study presentation, this article centres social justice values of lived experience leadership and involvement in research. This article aims to extend current knowledge and understanding of EDs in discordant twins, particularly regarding risk for ED development, ED duration, diagnosis and treatment, and recovery processes.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted.

Association between adolescent alcohol use and cognitive function in young adulthood: A co-twin comparison study.

Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders. A random effects model accounting for nesting in families was used to control for measured confounders. Next, co-twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co-twins. Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland. Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use. Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co-twin control [freq: stnd beta = -0.12, 95% confidence interval (CI) = -0.234, -0.013] and MZ only co-twin control models (freq: stnd beta = -0.305, 95% CI = -0.523, -0.087; intox: stnd beta = -0.301, 95% CI = -0.528, -0.074). In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores.

Monozygotic twins discordant for depression: An extended network comparison of depressive symptoms, cognitive functions and daily activities

Monozygotic twins share the same genotype; however, they can be phenotypically discordant on various traits. Studying discordant monozygotic twins allows the investigation of differences in associations between symptoms and psychopathological risk factors, controlled for shared genetic liability. The network approach to psychopathology suggests that depressive symptoms, along with risk and protective factors (e.g., cognition, daily activities), form a complex system of mutually interacting components. We compared monozygotic twins discordant for lifetime depression on their respective extended networks of depressive symptoms, cognitive functions and daily activities (intellectual, physical, social), and evaluated if these networks differ in their associations between variables and in the role of each variable within the network. Regularized partial correlations investigated the networks' composition in 147 monozygotic twin pairs discordant for depression from the Danish Twin Registry. Affected twins had stronger overall associations within their network of depressive symptoms, cognitive functions and daily activities than their unaffected co-twins, while the importance of the network components’ associations did not differ between the co-twins. In affected twins, decreased frequency in experiencing happiness had the strongest association with remaining variables (i.e., the most influence in activating other network elements). Also, variables from different groups were significantly associated (e.g., loneliness with delayed memory, pessimism with low social activities, verbal learning with intellectual activities). In unaffected twins, both mood symptoms and cognitive functions were important, but between-groups associations were quasi-absent. These results suggest that external events affecting the ability to feel happiness likely trigger the psychopathological process (depression network activation), independently from the genetic predisposition to depression.

NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.