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Zhonghua Er Bi Yan Hou Tou Jing Wai Ke... Mar 2024
Topics: Humans; Twins, Monozygotic; Head; Rhabdomyosarcoma; Neck; Head and Neck Neoplasms; Combined Modality Therapy
PubMed: 38561268
DOI: 10.3760/cma.j.cn115330-20230827-00063 -
Development and Psychopathology Apr 2024The present study examined the longitudinal associations between three dimensions of temperament - activity, affect-extraversion, and task orientation - and childhood...
The present study examined the longitudinal associations between three dimensions of temperament - activity, affect-extraversion, and task orientation - and childhood aggression. Using 131 monozygotic and 173 dizygotic (86 same-sex) twin pairs from the Louisville Twin Study, we elucidated the ages, from 6 to 36 months, at which each temperament dimension began to correlate with aggression at age 7. We employed latent growth modeling to show that developmental increases (i.e., slopes) in activity were positively associated with aggression, whereas increases in affect-extraversion and task orientation were negatively associated with aggression. Genetically informed models revealed that correlations between temperament and aggression were primarily explained by common genetic variance, with nonshared environmental variance accounting for a small proportion of each correlation by 36 months. Genetic variance explained the correlations of the slopes of activity and task orientation with aggression. Nonshared environmental variance accounted for almost half of the correlation between the slopes of affect-extraversion and aggression. Exploratory analyses revealed quantitative sex differences in each temperament-aggression association. By establishing which dimensions of temperament correlate with aggression, as well as when and how they do so, our work informs the development of future child and family interventions for children at highest risk of aggression.
PubMed: 38557599
DOI: 10.1017/S0954579424000634 -
Stem Cell Research Jun 2024Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems...
Leber hereditary optic neuropathy (LHON) is one of the most common mitochondrial illness, causing retinal ganglion cell degeneration and central vision loss. It stems from point mutations in mitochondrial DNA (mtDNA), with key mutations being m.3460G > A, m.11778G > A, and m.14484 T > C. Fibroblasts from identical twins, sharing m.14484 T > C and m.10680G > A variants each with 70 % heteroplasmy, were used to generate iPSC lines. Remarkably, one twin, a LHON patient, displayed symptoms, while the other, a carrier, remained asymptomatic. These iPSCs offer a valuable tool for studying factors influencing disease penetrance and unravelling the role of m.10680G > A, which is still debated.
Topics: Humans; Optic Atrophy, Hereditary, Leber; Induced Pluripotent Stem Cells; Twins, Monozygotic; DNA, Mitochondrial; Male; Mitochondria; Female; Point Mutation; Adult
PubMed: 38552355
DOI: 10.1016/j.scr.2024.103406 -
Journal of Surgical Case Reports Mar 2024Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world...
Studies in monozygotic (MZ) twins may help researchers elucidate the complex relationships between genetic and environmental factors on weight loss. We present a world first of MZ twins who have undergone the single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) procedure who have identical weights 3 years post-operatively. Two MZ twin 49-year-old females were assessed preoperatively and were indicated for the SADI-S procedure. They underwent surgery in 2020 by the same surgical team. Three years later post-operatively they had identical weights of 62 kg (and a BMI of 23) and %EWL of 126 and 124% respectively. SADI-S is a novel bariatric procedure for morbid obesity. Studies have found concordant epigenetic patterns in patients who have undergone bariatric surgery as well as MZ twins who have hypocaloric diets. Genetics exert a strong influence in weight management. Surgical management as well as a collaborative multidisciplinary approach is beneficial in supporting long lasting weight loss in bariatric surgery.
PubMed: 38549721
DOI: 10.1093/jscr/rjae192 -
Metabolites Mar 2024Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We...
Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy-Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in (p.Arg565Trp) and a novel variant in (p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without contractures, respectively. The twins exhibited symptoms that overlapped with both of these conditions. The results of the untargeted metabolomics analysis revealed significant metabolic perturbations relating to neurodevelopmental abnormalities, kidney dysfunction, and microbiome. The significant metabolites belong to essential pathways such as lipids and amino acid metabolism. The identification of variants in two genes, combined with the support of metabolic perturbation, demonstrates the rarity and complexity of this phenotype and provides valuable insights into its underlying mechanisms.
PubMed: 38535312
DOI: 10.3390/metabo14030152 -
Med (New York, N.Y.) Apr 2024In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk...
BACKGROUND
In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets.
METHODS
In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data. We verified functional characteristics by exploring the role of therapy and performed separate analyses in unrelated individuals.
FINDINGS
The frequencies of CXCR3 memory B cells were reduced in the blood of genetically identical twins with MS compared to their unaffected twin siblings. Natalizumab (anti-VLA-4 antibody) was the only treatment regimen under which these frequencies were reversed. The CNS-homing features of CXCR3 memory B cells were supported by elevated CXCL10 levels in MS cerebrospinal fluid and their in vitro propensity to develop into antibody-secreting cells.
CONCLUSIONS
Circulating CXCR3 memory B cells are affected by non-heritable cues in people who develop MS. This underlines the requirement of environmental risk factors such as Epstein-Barr virus in triggering these B cells. We propose that after CXCL10-mediated entry into the CNS, CXCR3 memory B cells mature into antibody-secreting cells to drive MS.
FUNDING
This work was supported by Nationaal MS Fonds (OZ2021-016), Stichting MS Research (19-1057 MS, 20-490f MS, and 21-1142 MS), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program grant agreement no. 882424, and the Swiss National Science Foundation (733 310030_170320, 310030_188450, and CRSII5_183478).
Topics: Humans; Multiple Sclerosis; Memory B Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Natalizumab; Receptors, CXCR3
PubMed: 38531361
DOI: 10.1016/j.medj.2024.02.013 -
Acta Ophthalmologica Mar 2024To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.
PURPOSE
To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.
METHODS
In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis.
RESULTS
Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172-0.688, p < 0.01).
CONCLUSION
A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.
PubMed: 38528623
DOI: 10.1111/aos.16671 -
NeuroImage. Clinical 2024Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus,...
OBJECTIVE
Intracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS.
METHODS
FSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV.
RESULTS
54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003).
CONCLUSION
We offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.
Topics: Humans; Adult; Female; Male; Twins, Monozygotic; Magnetic Resonance Imaging; Multiple Sclerosis; Middle Aged; Brain; Young Adult; Age of Onset; Organ Size
PubMed: 38522363
DOI: 10.1016/j.nicl.2024.103597 -
Medecine Sciences : M/S Mar 2024Rare unrelated individuals show striking resemblance, almost as high as monozygotic twins. Extensive genetic analysis of a set of such individuals shows that every...
Rare unrelated individuals show striking resemblance, almost as high as monozygotic twins. Extensive genetic analysis of a set of such individuals shows that every couple shares a given allele at a large set of loci, enriched for "face genes". The similarity is limited to this set of loci, and the rest of the genome is quite diverse in these "look alike" individuals.
Topics: Humans; Twins, Monozygotic; Genome, Human
PubMed: 38520107
DOI: 10.1051/medsci/2024016 -
Molecular Psychiatry Mar 2024Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune...
Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Aberrant activation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes compared to healthy individuals. Microglia from affected twins had also reduced response to interleukin 1 beta (IL1β) treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent Gene Ontology (GO) terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of major histocompatibility complex (MHC) class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have gene expression aberrations related to inflammation response and extracellular matrix without contributing to increased microglial activation.
PubMed: 38519640
DOI: 10.1038/s41380-024-02529-1