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Molecular Psychiatry May 2024Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder....
Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.
PubMed: 38704507
DOI: 10.1038/s41380-024-02561-1 -
Twin Research and Human Genetics : the... Apr 2024TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and...
TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country's population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.
Topics: Humans; Mexico; Male; Female; Gene-Environment Interaction; Registries; Adult; Diseases in Twins; Middle Aged; Twins, Monozygotic; Twins, Dizygotic; Mental Disorders; Cardiovascular Diseases
PubMed: 38699821
DOI: 10.1017/thg.2024.18 -
BMC Pregnancy and Childbirth May 2024To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived... (Comparative Study)
Comparative Study
Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.
OBJECTIVE
To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally.
METHODS
We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally.
RESULT
MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05).
CONCLUSION
Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.
Topics: Humans; Female; Pregnancy; Pregnancy, Twin; Reproductive Techniques, Assisted; Pregnancy Outcome; Retrospective Studies; Adult; Twins, Monozygotic; Chorion; Premature Birth; Twins, Dizygotic; Infant, Newborn; Placenta Previa
PubMed: 38698326
DOI: 10.1186/s12884-024-06521-z -
International Journal of Surgery Case... Jun 2024Posterior cruciate ligament (PCL) tears are not as frequent as anterior cruciate ligament (ACL) tears. They are rare as an isolated injury and more commonly occur in a...
INTRODUCTION AND IMPORTANCE
Posterior cruciate ligament (PCL) tears are not as frequent as anterior cruciate ligament (ACL) tears. They are rare as an isolated injury and more commonly occur in a multi-ligament-injured knee. We reported a case of rupture of PCL in monozygotic twins.
CASE PRESENTATION
A 19-year-old female presented with giving away of her left knee since 4 months ago. She fell from stairs previously. Physical examination demonstrated positive posterior drawer test. Magnetic resonance imaging showed ruptured PCL and lateral meniscal tear. Two months later, her identical twin, also a 19-year old-female, fell from the stairs and complained of giving away. Physical examination showed positive posterior drawer test. Magnetic resonance imaging demonstrated ruptured PCL and lateral meniscal tear. Both patients underwent arthroscopic-assisted PCL reconstruction using gracilis, semitendinosus, and peroneus tendon graft. At one year of follow-up, there were no graft failures. The twins had satisfactory outcome measured by Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). Both were athletes prior to their injury and they returned to sport.
CLINICAL DISCUSSION
Although it has never been reported before, this report shows that patients may have genetic predisposition to the incidence of PCL rupture. This is likely because of heritable factors, such as biomechanical, anatomic, anthropometric, and neuromuscular traits. A family history of PCL tear may increase the risk of a PCL tear. Further studies are recommended to examine genetic variants as a risk factor for PCL tears and other knee disorders.
CONCLUSIONS
Multiple variables may lead to the increased risk of these twins: the combination of improper neuromuscular control, genetic factors, and possibly hormonal factors contributed to their PCL injuries. Further history exploration, lab tests, and genetic analysis should be done to determine the variables. Both patients returned to sports protocol testing and returned to sports one year postoperatively.
PubMed: 38688154
DOI: 10.1016/j.ijscr.2024.109682 -
Journal of Atherosclerosis and... Apr 2024A twin study is a valuable tool for elucidating the acquired factors against lifestyle diseases such as dyslipidemia, diabetes mellitus, and obesity. We aimed 1. to...
AIM
A twin study is a valuable tool for elucidating the acquired factors against lifestyle diseases such as dyslipidemia, diabetes mellitus, and obesity. We aimed 1. to investigate the factors that affect low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in monozygotic (MZ) twins, and 2. to identify genes which expression levels changed in pairs with large differences in LDL-C or HDL-C levels.
METHODS
The registered database at the Center for Twin Research, Osaka University, containing 263 pairs of MZ twins, was analyzed. 1. The effects of smoking, exercise, nutritional factors, and anthropometric and biochemical parameters on LDL-C or HDL-C levels were examined in MZ twins. 2. RNA sequencing in the peripheral blood mononuclear cells of 59 pairs was analyzed for large differences of LDL-C or HDL-C groups.
RESULTS
1. The ΔLDL-C levels were significantly associated with an older age, the ΔTG levels, and ΔBMI. ΔHDL-C levels were associated with the ΔBMI, ΔTG, ΔTP, and ΔLDL-C levels. The HDL-C levels were affected by smoking and exercise habits. The intakes of cholesterol and saturated fatty acids were not associated with the LDL-C or HDL-C levels. 2. An RNA sequencing analysis revealed that the expression of genes related to the TLR4 and IFNG pathways was suppressed in accordance with the HDL-C levels in the larger ΔHDL-C group among the 59 pairs.
CONCLUSION
We identified the factors affecting the LDL-C or HDL-C levels in monozygotic twins. In addition, some types of inflammatory gene expression in peripheral blood mononuclear cells were suppressed in accordance with the HDL-C levels, thus suggesting the importance of weight management and exercise habits in addition to dietary instructions to control the LDL-C or HDL-C levels.
PubMed: 38684403
DOI: 10.5551/jat.64882 -
Genes Apr 2024The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of...
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.
Topics: Humans; Female; Aged; Male; Aged, 80 and over; Aging; Twins, Dizygotic; Twins, Monozygotic; Gene Expression
PubMed: 38674429
DOI: 10.3390/genes15040495 -
Journal of Clinical Medicine Apr 2024: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially...
: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel therapeutic approaches. We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR). The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L, = 0.037). The present study could benefit from a larger sample size. We did not assess dietary habits. The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.
PubMed: 38673634
DOI: 10.3390/jcm13082361 -
PloS One 2024Neighbourhood deprivation has been found to be associated with many health conditions, but its association with low back pain (LBP) and arthritis is unclear. This study...
OBJECTIVE
Neighbourhood deprivation has been found to be associated with many health conditions, but its association with low back pain (LBP) and arthritis is unclear. This study aimed to examine the association between neighbourhood deprivation with LBP and arthritis, and its potential interaction with individual socioeconomic status (SES) on these outcomes.
METHODS
Monozygotic (MZ) twins from the Washington State Twin Registry were used to control for genetic and common environmental factors that could otherwise confound the purported relationship. Multilevel models were employed to examine the association between neighbourhood deprivation as well as individual-level SES with LBP/arthritis, adjusting for age, sex, body mass index (BMI) and residence rurality.
RESULTS
There were 6,380 individuals in the LBP sample and 2,030 individuals in the arthritis sample. Neighbourhood deprivation was not associated with LBP (P = 0.26) or arthritis (P = 0.61), and neither was its interaction with individual-level SES. People without a bachelor's degree were more likely to report LBP (OR 1.44, 95% CI 1.26-1.65) or both LBP and arthritis (OR 1.67, 95% CI 1.14-2.45) than those with a bachelor's degree, but not for arthritis alone (P = 0.17). Household income was not significantly associated with LBP (P = 0.16) or arthritis (p = 0.23) independent of age, sex, and BMI.
CONCLUSION
Our study did not find significant associations between neighbourhood deprivation and the presence of LBP or arthritis. More research using multilevel modelling to investigate neighbourhood effects on LBP and arthritis is recommended.
Topics: Humans; Low Back Pain; Male; Female; Middle Aged; Adult; Arthritis; Residence Characteristics; Twins, Monozygotic; Social Class; Washington; Aged
PubMed: 38669221
DOI: 10.1371/journal.pone.0298356 -
Frontiers in Human Neuroscience 2024This study examined brain functional connectivity (FC) changes associated with possible anomalous interactions between sensorily isolated monozygotic (MZ) twins. Brain...
This study examined brain functional connectivity (FC) changes associated with possible anomalous interactions between sensorily isolated monozygotic (MZ) twins. Brain FC was estimated using the Steady State Visual Evoked Potential-Event Related Partial Coherence (SSVEP-ERPC) methodology. Five twin pairs served twice as participants, with an average interval between sessions of 67 days. In each recording session, one twin, the Sender, viewed a randomized set of 50 general images and 50 personally relevant images, while the other twin, the Receiver, viewed a static personally relevant image for the entire duration of the session. Images appeared on the Sender screen for 1.0 s, with the interval between successive images varied randomly between 4.0 and 8.0 s. Receiver FC changes were calculated based on the appearance times of the images as viewed by the Sender. It was hypothesized that anomalous interactions would be indicated by statistically significant Receiver FC changes when those changes are determined using the Sender image appearance times. For each twin serving as Receiver, FC components were separately analyzed for the 50 general and the 50 personal images, yielding 38 observations (19 twin pairs by 2 conditions). The hypothesis was confirmed in that 11 of the 38 observations yielded statistically significant Receiver FC increases or decreases at the < 0.01 level only when trials were synchronized to the Sender image appearance times. Overall, this effect was significant at the = 4 × 10 Df = 175. To the best of our knowledge, this is the first study reporting statistically significant FC changes indicative of anomalous interactions between two sensorily isolated individuals.
PubMed: 38660011
DOI: 10.3389/fnhum.2024.1388049 -
Journal of Human Genetics Apr 2024Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59...
Handgrip strength is a crucial indicator to monitor the change of cognitive function over time, but its mechanism still needs to be further explored. We sampled 59 monozygotic twin pairs to explore the potential mediating effect of DNA methylation (DNAm) on the association between handgrip strength and cognitive function. The initial step was the implementation of an epigenome-wide association analysis (EWAS) in the study participants, with the aim of identifying DNAm variations that are associated with handgrip strength. Following that, we conducted an assessment of the mediated effect of DNAm by the use of mediation analysis. In order to do an ontology enrichment study for CpGs, the GREAT program was used. There was a significant positive association between handgrip strength and cognitive function (β = 0.194, P < 0.001). The association between handgrip strength and DNAm of 124 CpGs was found to be statistically significant at a significance level of P < 1 × 10. Fifteen differentially methylated regions (DMRs) related to handgrip strength were found in genes such as SNTG2, KLB, CDH11, and PANX2. Of the 124 CpGs, 4 within KRBA1, and TRAK1 mediated the association between handgrip strength and cognitive function: each 1 kg increase in handgrip strength was associated with a potential decrease of 0.050 points in cognitive function scores, mediated by modifications in DNAm. The parallel mediating effect of these 4 CpGs was -0.081. The presence of DNAm variation associated with handgrip strength may play a mediated role in the association between handgrip strength and cognitive function.
PubMed: 38649436
DOI: 10.1038/s10038-024-01247-4