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PloS One 2023The relationship between obesity and mental health is complex and is moderated by the level of obesity, age, sex, and social and genetic factors. In the current study,...
OBJECTIVE
The relationship between obesity and mental health is complex and is moderated by the level of obesity, age, sex, and social and genetic factors. In the current study, we used a unique co-twin control design, with twin pairs discordant for body mass index (BMI), to control for shared genetic and environmental effects between obesity and several dimensions of mental health.
METHODS
We studied 74 monozygotic (MZ) twin pairs, of whom 36 were BMI-discordant (intra-pair difference in BMI ≥ 3 kg/m2), and 77 dizygotic (DZ) twin pairs (46 BMI-discordant). We assessed subjective health, especially mental health and mental well-being (depression, anxiety, self-esteem, health-related quality of life, life satisfaction, and social well-being) through questionnaires.
RESULTS
Heavier MZ co-twins from BMI-discordant pairs had poorer general health (58.8±3.0 vs. 72.4±3.8, P = 0.001, FDR = 0.017 on a scale from 0 to 100 where higher scores indicate more positive results), physical functioning (90.3±1.1 vs. 95.5±2.2, P = 0.024, FDR = 0.122), energy levels (55.6±3.4 vs. 66.6±3.3, P = 0.013, FDR = 0.109), and emotional well-being (65.9±3.2 vs. 75.4±2.9, P = 0.031, FDR = 0.122), as well as a tendency for depressive symptoms (8.4±1.3 vs. 5.6±0.9, P = 0.071, FDR = 0.166) compared to their leaner co-twins. Heavier DZ co-twins had poorer total physical well-being (91.6±1.9 vs. 95.6±1.0, P = 0.035, FDR = 0.356) and more depressive symptoms (4.3±0.9 vs. 2.4±0.5, P = 0.016, FDR = 0.345 on a scale from 0 to 63 where lower scores indicate fewer depressive symptoms) than their leaner co-twins. Association analyses, using all twin pairs, confirmed that higher BMI within pairs linked to general health, physical functioning and depressive symptoms. No association was found between BMI and anxiety, self-esteem, life satisfaction, or social well-being.
CONCLUSIONS
In conclusion, this study underscores the notable association between elevated BMI and physical well-being and to a lesser extent between elevated BMI and depressive symptoms, while revealing no discernible connections with anxiety, self-esteem, life satisfaction, or social well-being.
Topics: Humans; Young Adult; Body Mass Index; Health Status; Obesity; Quality of Life; Twins, Dizygotic; Twins, Monozygotic
PubMed: 38055659
DOI: 10.1371/journal.pone.0294162 -
Child's Nervous System : ChNS :... Mar 2024We present a unique case of monozygotic female twins with virtually identical clinical and radiological presentations of supratentorial hydrocephalus and cystic...
INTRODUCTION
We present a unique case of monozygotic female twins with virtually identical clinical and radiological presentations of supratentorial hydrocephalus and cystic formations from the suprasellar cistern.
DISCUSSION
Evaluating genetic predispositions and prenatal exposures is crucial for hydrocephalus in twins. Familial cases imply a genetic contribution to the development of these anomalies, including chromosomal abnormalities and specific variants linked to arachnoid cyst formation in various syndromes. Extensive genetic analyses found no pathogenic variants in the twins. Prenatal exposure to anti-epileptic medication was known during pregnancy and may be associated with fetal abnormalities, but not central nervous system (CNS) malformations, and was therefore not considered the cause of the condition in the twins. The twins presenting simultaneously with hydrocephalus caused by suprasellar cysts (SAC) underwent a two-step surgical management: initial ventriculoperitoneal shunt (VPS) placement followed by fenestration. Postoperative imaging showed cyst reduction, but a secondary VPS was necessary in both cases.
CONCLUSION
Genetic analysis is less likely to identify a monogenic etiology in non-syndromic cases of SACs, which are assumed to be multifactorial. There is no established evidence linking a teratogenic effect of anti-epileptic drugs to CNS malformations. Moreover, the surgical treatment of this complex condition constitutes a point of discussion.
Topics: Pregnancy; Female; Humans; Hydrocephalus; Arachnoid Cysts; Anticonvulsants; Genetic Predisposition to Disease; Postoperative Period
PubMed: 38052889
DOI: 10.1007/s00381-023-06245-z -
Human Reproduction (Oxford, England) Jan 2024Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast,... (Meta-Analysis)
Meta-Analysis
Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins.
Topics: Female; Humans; Pregnancy; Fertilization; Genetic Association Studies; Retrospective Studies; Twins, Dizygotic; Twins, Monozygotic; Infant, Newborn
PubMed: 38052159
DOI: 10.1093/humrep/dead131 -
Genome Biology Dec 2023Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking...
BACKGROUND
Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology).
RESULTS
The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity-including those located at long repeat regions, complex structural variants, and de novo mutations-are systematically examined in this study.
CONCLUSIONS
In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.
Topics: Humans; Benchmarking; East Asian People; Genomics; Haplotypes; High-Throughput Nucleotide Sequencing; Sequence Analysis, DNA; Twins, Monozygotic; Twin Studies as Topic
PubMed: 38049885
DOI: 10.1186/s13059-023-03116-3 -
BMC Pregnancy and Childbirth Nov 2023The main purpose of the present study was to investigate the correlation between placental anastomosis and superficial vascular branches in selective fetal growth...
INTRODUCTION
The main purpose of the present study was to investigate the correlation between placental anastomosis and superficial vascular branches in selective fetal growth restriction (sFGR) in monochorionic diamniotic twins.
MATERIALS AND METHODS
This was a retrospective analysis of the pregnancy data and placental perfusion of 395 patients with monochorionic diamniotic (MCDA) twin pregnancies delivered at our hospital from April 2013 to April 2020. We divided the patients into two groups and compared the number of placental superficial vascular branches in sFGR twins and normal MCDA twins. The correlation between the placental anastomosis and the number of superficial vascular branches in sFGR and normal MCDA twins was also investigated.
RESULTS
The number of umbilical arterial branches and umbilical venous branches was less than larger twins in sFGR, larger twins in normal MCDA and smaller twins in normal MCDA. (11.83 [4-44], 21.82 [7-50], 19.72 [3-38], 14.85 [0-31], p < 0.001, 6.08 [1-18], 9.60 [3-22], 9.96 [2-22], 8.38 [1-20], p < 0.00) For smaller twins in the sFGR group, the number of umbilical venous branches was positively associated with AA anastomosis overall diameter, AV anastomosis overall diameter and all anastomosis overall diameter. (r = 0.194, 0.182 and 0.211, p < 0.05) CONCLUSIONS: The risk of sFGR may arise when the placenta from MCDA twins shows a poor branching condition of placental superficial vessels. For the smaller twin of sFGR, regular ultrasound examination of the number of the umbilical venous branches may help to predict artery-to-artery (AA) overall diameter, artery-to-vein (AV) overall diameter and all anastomosis overall diameter.
Topics: Pregnancy; Humans; Female; Placenta; Fetal Growth Retardation; Retrospective Studies; Twins, Monozygotic; Pregnancy, Twin; Umbilical Arteries
PubMed: 38037010
DOI: 10.1186/s12884-023-06157-5 -
JAMA Network Open Nov 2023Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).
OBJECTIVE
To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.
INTERVENTION
Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.
MAIN OUTCOMES AND MEASURES
The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.
RESULTS
A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05297825.
Topics: Adult; Female; Humans; Male; Body Weight; Cardiovascular Diseases; Cholesterol, LDL; Diet, Vegan; Insulins; Twins, Monozygotic; Vegetables; Middle Aged; Diet, Healthy
PubMed: 38032644
DOI: 10.1001/jamanetworkopen.2023.44457 -
Tobacco Prevention & Cessation 2023Nicotine-containing products (NCPs) such as electronic nicotine delivery systems (ENDS) are increasingly common throughout the landscape of youth use of...
INTRODUCTION
Nicotine-containing products (NCPs) such as electronic nicotine delivery systems (ENDS) are increasingly common throughout the landscape of youth use of nicotine-containing products (NCP), and have overtaken traditional cigarette smoking modalities. This study seeks to examine the genetic and environmental influences on liability for susceptibility and initiation of ENDS and other NCPs among US children.
METHODS
Data were drawn from 886 monozygotic (MZ) and dizygotic (DZ) twin pairs aged 9-10 years in the Adolescent Brain & Cognitive Development (ABCD) study at the baseline during 2016-2018. Heritability (h) measured the proportion of the total phenotypic variation attributable to genes. Variance component models were utilized to analyze influences from the common environment (c) and unique environmental factors (e), taking into account correlations within twin pairs.
RESULTS
The national sample included 50% females, 69.5% of non-Hispanic Whites, 12.8% of non-Hispanic Blacks, and 11.6% of Hispanics, with a mean age of 121.5 months. The twin sets were 60% DZ and 40% MZ. Heritability was low for NCP susceptibility (h=0) and moderate for NCP initiation (h=39%, p=0.02). The variance associated with NCP susceptibility was primarily influenced by environmental factors, especially one's unique factors (c=37%, p<0.0001 vs e=63%, p<0.0001). In contrast, the variance associated with NCP initiation was split across common and unique environmental factors (c=32%, p=0.02 vs e=29%, p=0.02).
CONCLUSIONS
In the era with ENDS use surging among youth, NCP initiation remains to be a heritable trait with joint influence from the environment. NCP susceptibility is largely influenced by environmental factors, especially unique environments. Continued assessment of gene × environment interaction can better inform future youth NCP interventions.
PubMed: 38026821
DOI: 10.18332/tpc/173556 -
Global Pediatric Health 2023Fetus in fetu is an uncommon medical anomaly characterized by the presence of a malformed fetus within the body of a living twin. Although the retroperitoneum is the...
Fetus in fetu is an uncommon medical anomaly characterized by the presence of a malformed fetus within the body of a living twin. Although the retroperitoneum is the most typical location, occurrences in the sacrococcygeal and dorsolumbar regions are rare. Ongoing debates center around its embryopathogenesis, debating whether it is a highly specialized teratoma or a result of parasitic twinning in a monozygotic monochorionic diamniotic pregnancy. Notably, distinguishing factors such as vertebral bodies and limbs are pivotal in discerning FIF from teratomas. Diagnostic imaging techniques are integral for preoperative diagnosis, with histopathological examination confirming the condition's presence.
PubMed: 38024466
DOI: 10.1177/2333794X231210621 -
Genome Biology Nov 2023Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate...
BACKGROUND
Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.
RESULTS
We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data.
CONCLUSIONS
The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.
Topics: Humans; Reproducibility of Results; Genome, Human; Benchmarking; Polymorphism, Single Nucleotide; Germ Cells; High-Throughput Nucleotide Sequencing
PubMed: 38012772
DOI: 10.1186/s13059-023-03109-2 -
A diagnostic conundrum in Bardet-Biedl syndrome: when genetic diagnosis precedes clinical diagnosis.Endocrinology, Diabetes & Metabolism... Oct 2023Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod-cone dystrophy,...
SUMMARY
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod-cone dystrophy, early-onset obesity and related complications, postaxial polydactyly, renal and genitourinary abnormalities, learning disabilities, and hypogonadism. The diagnosis is based on Beales' modified diagnostic criteria. We present a case of two monozygotic female twins, 17 years of age at presentation, referred for obesity since childhood. The initial hormonal work-up was negative and no dysmorphic features were noted. They were diagnosed with exogenous obesity. However, after ophthalmologic problems became apparent, rod-cone dystrophy was observed and genetic testing was performed. A mutation in the BBS2 gene led to the diagnosis of BBS, although the full diagnostic criteria were not met. This case not only highlights the need to raise awareness for BBS but also exposes two limitations of the current diagnostic standard. The first limitation is the low sensitivity of the clinical diagnostic model, due to the progressive onset and the high variability of the syndrome. The second limitation is the unclear role of genetic testing. As genetic testing becomes more widely available, genetic diagnosis preceding clinical diagnosis will become more common, leading to a diagnostic conundrum. We propose an update of the diagnostic model. A less strict application in the presence of confirmed genetic mutations should be applied, as this could facilitate earlier diagnosis and intervention. This is important because therapeutic agents are being developed that could have a significant impact on quality of life and prognosis.
LEARNING POINTS
Due to the low prevalence, the significant inter-and intrafamilial variation, and the slowly evolving phenotype, monogenic forms of obesity such as Bardet-Biedl syndrome are difficult to diagnose. Despite advances in the understanding of the presentation, pathophysiology and access to accurate genetic characterisation, a substantial number of diagnoses are still made by ophthalmology, as recognition of BBS in other departments of medicine, remains limited. Clinical diagnosis of BBS is based on Beales' modified diagnostic criteria which require the presence of four primary features or three primary features plus two secondary features. This model has its limitations. Due to the progressive onset of clinical symptoms, patients generally do not meet the diagnostic criteria early in life, leading to a delay in diagnosis. In addition, the role of genetic testing remains controversial. However, as it becomes more widely available, genetic diagnosis may precede a full clinical diagnosis. BBS has an impact on the quality of life and prognosis of both the patient and the family. Obesity management strategies are an important part of the multidisciplinary approach, as there is no cure available. Setmelanotide has shown promising results in a phase 3 trial, but its effect in clinical practice remains unproven.
PubMed: 37997784
DOI: 10.1530/EDM-23-0055