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Behavior Genetics Jul 2024Subjective health ratings are associated with dementia risk such that those who rate their health more poorly have increased risk for dementia. The genetic and...
Subjective health ratings are associated with dementia risk such that those who rate their health more poorly have increased risk for dementia. The genetic and environmental mechanisms underlying this association are unclear, as prior research cannot rule out whether the association is due to genetic confounds. The current study addresses this gap in two samples of twins, one from Sweden (N = 548) and one from Denmark (N = 4,373). Using genetically-informed, bivariate regression models, we assessed whether additive genetic effects explained the association between subjective health and dementia risk as indexed by a latent variable proxy measure. Age at intake, sex, education, depressive symptomatology, and follow-up time between subjective health and dementia risk assessments were included as covariates. Results indicate that genetic variance and other sources of confounding accounted for the majority of the effect of subjective health ratings on dementia risk. After adjusting for genetic confounding and other covariates, a small correlation was observed between subjective health and latent dementia risk in the Danish sample (r = - .09, p < .05). The results provide further support for the genetic association between subjective health and dementia risk, and also suggest that subjective ratings of health measures may be useful for predicting dementia risk.
Topics: Humans; Dementia; Female; Male; Sweden; Denmark; Aged; Aging; Risk Factors; Health Status; Middle Aged; Aged, 80 and over; Twins, Monozygotic; Prospective Studies; Twins, Dizygotic; Self Report
PubMed: 38822218
DOI: 10.1007/s10519-024-10182-1 -
Psychoneuroendocrinology May 2024Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with...
Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients.
BACKGROUND/OBJECTIVE
Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS).
METHODS
46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire.
RESULTS
From the parents' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, β=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, β=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, β=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001).
CONCLUSION
Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents' perspective on the smaller twins' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.
PubMed: 38810374
DOI: 10.1016/j.psyneuen.2024.107082 -
Neuromuscular Disorders : NMD Jul 2024We report on genetic and environmental modulation of social cognition abilities and brain volume correlates in two monozygotic twins (Twin1 and Twin2) with genetically...
Different neuropsychological and brain volumetric profiles in a pair of identical twins with myotonic dystrophy type 1 indicate a non-genetic modulation of clinical phenotype.
We report on genetic and environmental modulation of social cognition abilities and brain volume correlates in two monozygotic twins (Twin1 and Twin2) with genetically confirmed myotonic dystrophy-type1 who grew up in different environmental settings. They both underwent neuropsychological assessment (i.e., Intelligent Quotient [IQ], theory of mind, emotion recognition tests), and MRI scanning to evaluate regional brain volumetrics compared to 10 gender and sex-matched healthy controls. Against a normal IQ level in both patients, Twin1 was more impaired in emotional processing and Twin2 in cognitive aspects of social cognition. Both patients showed grey matter (GM) atrophy in Brodmann Areas 23/31 (BA23/31) and BA7 bilaterally, while Twin2 showed additional GM loss in right BA46. Both patients showed a similar pattern of white matter atrophy involving the thalamus, basal ganglia, and uncinate fasciculus. White matter atrophy appeared to be mostly driven by genetics, while grey matter volumes appeared associated with different impairments in social cognition and possibly modulated by environment.
Topics: Humans; Myotonic Dystrophy; Twins, Monozygotic; Brain; Neuropsychological Tests; Male; Phenotype; Magnetic Resonance Imaging; Female; Adult; Atrophy; Gray Matter; Middle Aged; White Matter; Social Cognition
PubMed: 38810327
DOI: 10.1016/j.nmd.2024.04.007 -
Immunological Reviews May 2024Multiple sclerosis (MS) affects more than 2.8 million people worldwide but the distribution is not even. Although over 200 gene variants have been associated with... (Review)
Review
Multiple sclerosis (MS) affects more than 2.8 million people worldwide but the distribution is not even. Although over 200 gene variants have been associated with susceptibility, studies of genetically identical monozygotic twin pairs suggest that the genetic make-up is responsible for only about 20%-30% of the risk to develop disease, while the rest is contributed by milieu factors. Recently, a new, unexpected player has entered the ranks of MS-triggering or facilitating elements: the human gut microbiota. In this review, we summarize the present knowledge of microbial effects on formation of a pathogenic autoreactive immune response targeting the distant central nervous system and delineate the approaches, both in people with MS and in MS animal models, which have led to this concept. Finally, we propose that a tight combination of investigations of human patients with studies of suitable animal models is the best strategy to functionally characterize disease-associated microbiota and thereby contribute to deciphering pathogenesis of a complex human disease.
PubMed: 38809041
DOI: 10.1111/imr.13357 -
The Journal of Medicine and Philosophy May 2024It is often argued that certain metaphysical complications surrounding the phenomenon of monozygotic twinning force us to conclude that, prior to the point at which...
It is often argued that certain metaphysical complications surrounding the phenomenon of monozygotic twinning force us to conclude that, prior to the point at which twinning is no longer possible, the zygote or early embryo cannot be considered an individual human organism. In this essay, I argue, on the contrary, that there are in fact several ways of making sense of monozygotic twinning that uphold the humanity of the original zygote, but also that there is no easy answer to what happens when the human zygote twins. All of the options available carry with them one or more surprising, alarming, or otherwise counterintuitive implications. All things considered, I conclude that the "budding option," according to which the original human organism present before twinning carries on as one of the resulting embryos but not the other, is the most plausible explanation of what happens when a human zygote twins.
PubMed: 38805694
DOI: 10.1093/jmp/jhae022 -
Human Brain Mapping Jun 2024Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is...
Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is still being determined. Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum ( 47%-91%). Additionally, the good to excellent test-retest reliability for a subsample of QTIM participants suggests that non-genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome-wide association studies.
Topics: Humans; Cerebellum; Male; Adolescent; Female; Magnetic Resonance Imaging; Young Adult; Child; Adult; Organ Size; Twins, Monozygotic
PubMed: 38798116
DOI: 10.1002/hbm.26717 -
Journal of Clinical Immunology May 2024
Correction to: Monozygotic Twins with MAGT1 Deficiency and Epstein-Barr virus-positive Classic Hodgkin Lymphoma Receiving anti-CD30 CAR T-cell Immunotherapy: A case Report.
PubMed: 38795171
DOI: 10.1007/s10875-024-01723-8 -
Genes May 2024Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their... (Meta-Analysis)
Meta-Analysis
Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their genetic association and function in cognitive processes such as long-term potentiation. We conducted a systematic gene expression meta-analysis of four PDE4 genes (PDE4A-D) in 10 brain sample datasets (437 samples) and three blood sample datasets (300 samples). Subsequently, we measured mRNA levels in iPSC-derived hippocampal dentate gyrus neurons generated from fibroblasts of three groups: healthy controls, healthy monozygotic twins (MZ), and their MZ siblings with schizophrenia. We found downregulation of PDE4B in brain tissues, further validated by independent data of the CommonMind consortium (515 samples). Interestingly, the downregulation signal was present in a subgroup of the patients, while the others showed no differential expression or even upregulation. Notably, PDE4A, PDE4B, and PDE4D exhibited upregulation in iPSC-derived neurons compared to healthy controls, whereas in blood samples, PDE4B was found to be upregulated while PDE4A was downregulated. While the precise mechanism and direction of altered PDE4 expression necessitate further investigation, the observed multilevel differential expression across the brain, blood, and iPSC-derived neurons compellingly suggests the involvement of PDE4 genes in the pathophysiology of schizophrenia.
Topics: Schizophrenia; Humans; Cyclic Nucleotide Phosphodiesterases, Type 4; Induced Pluripotent Stem Cells; Neurons; Brain; Male; Female; Adult
PubMed: 38790238
DOI: 10.3390/genes15050609 -
Early Human Development Jul 2024Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study...
Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002-2020 were retrospectively reviewed for NEC. Potential risk factors for NEC were studied. For within-pair comparison, outcomes were compared between affected and unaffected twins. Within-pair analyses showed that the twin with NEC had a lower birth weight compared to its unaffected co-twin (1100 (913-1364) vs. 1339 (1093-1755) grams). Median gestational age at birth and birth weight were lower in twin pairs in the NEC-group compared to the no-NEC group, 29.1 weeks (27.8-30.8) versus 33.6 (30.7-36.0) and 1221 g (1010-1488) versus 1865 (1356-2355) respectively. Twin pregnancies in the NEC-group were more often complicated by twin-to-twin transfusion syndrome compared to the no-NEC-group (70 % (14/20) vs. 49 % (472/962)), particularly when treated with amnioreduction. This unique population of identical twins confirms that preterm neonates with a relatively lower birth weight are more prone to develop NEC compared to their co-twin, regardless of other genetic, maternal and obstetrical factors.
Topics: Humans; Enterocolitis, Necrotizing; Infant, Newborn; Female; Twins, Monozygotic; Male; Infant, Premature; Pregnancy; Case-Control Studies; Diseases in Twins; Risk Factors; Retrospective Studies; Birth Weight; Gestational Age
PubMed: 38781714
DOI: 10.1016/j.earlhumdev.2024.106052 -
BMC Medical Genomics May 2024Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are...
BACKGROUND
Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins.
METHODS
The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11.
RESULTS
The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006).
CONCLUSION
This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.
Topics: Humans; Twins, Monozygotic; Myosin Heavy Chains; Male; Genetic Association Studies; Infant, Newborn; Phenotype; Cardiac Myosins; Aortic Aneurysm, Thoracic; Ductus Arteriosus, Patent; Female; Mutation; Aortic Dissection
PubMed: 38773466
DOI: 10.1186/s12920-024-01908-5