Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Role of vitamins in epilepsy.

Epilepsy is a chronic neurological disorder that presents as recurrent, unprovoked seizures. Pharmacotherapy is the main treatment for epilepsy, but at least 30% of patients with epilepsy have pharmacoresistant epilepsy. Therefore, non-pharmacological treatments are still required. In addition to electrophysiological aberrations contributing to epileptogenesis and pathophysiology in epilepsy, neuroinflammation, oxidative stress, and metabolic derangement have been investigated as drug targets in the treatment of epilepsy. Vitamins have antioxidant, anti-inflammatory, and immunomodulatory effects, which can be beneficial for the treatment of epilepsy. Herein, we comprehensively review the role of vitamins in epilepsy. Certain epilepsies are vitamin-dependent or vitamin-responsive. Most studies on vitamins in epilepsy are of low evidence level or limited to animal studies. Nevertheless, vitamin supplementation should be considered in epilepsy therapy. Additionally, certain anti-seizure medications may alter the serum levels of certain vitamins. Monitoring the serum levels of vitamins and supplementing vitamins when needed are suggested during the follow-up of patients with epilepsy.

Kawasaki Disease May Increase the Risk of Subsequent Cerebrovascular Disease.

BACKGROUND: Previous epidemiological investigations examining the association between Kawasaki disease (KD) and cerebrovascular disease have had conflicting results. We analyzed the association between KD and cerebrovascular disease by conducting a population-based retrospective cohort study designed to investigate the hypothesis that KD could be a risk factor for subsequent cerebrovascular disease. METHODS: From the National Health Insurance Research Database of Taiwan, the data of children (aged 0-18 years old) with KD (n=8467) were collected. Starting with the first year of study observation (referred to as the baseline year), data was collected for each child with KD, and 4 non-KD patients matched for sex, urbanization level of residence, and parental occupation were randomly selected to form the non-KD cohort (n=33 868) for our analysis. For the period from January 1, 2000, to December 31, 2012, we calculated the follow-up person-years for each patient, which is the time from the index date to the diagnosis of cerebrovascular disease, death, or the end of 2012. Furthermore, we compared the incidence, the incidence rate ratio, and the 95% CI of cerebrovascular disease between the KD and non-KD cohorts. RESULTS: The overall cerebrovascular disease incidence rate was found to be 3.19-fold higher, which is significantly higher, in the KD cohort than in the non-KD cohort (14.73 versus 4.62 per 100 000 person-years), and the overall risk of cerebrovascular disease remained higher in the KD cohort (adjusted hazard ratio, 3.16 [95% CI, 1.46-6.85]). Furthermore, children aged <5 years showed a significantly higher risk of subsequent cerebrovascular disease in the KD cohort (adjusted hazard ratio, 3.14 [95% CI, 1.43-6.92]). CONCLUSIONS: This nationwide retrospective cohort study shows that KD may increase the risk of subsequent cerebrovascular disease, especially in those with KD aged <5 years old.

Incidence of epilepsy in children born prematurely and small for gestational age at term gestation: A population-based cohort study.

AIM: This study assessed the incidence of epilepsy in preterm infants and those small for gestational age (SGA) at term and identified risk factors associated with higher epilepsy incidence in these children. METHODS: We enrolled children (from 2000 to 2010) who were premature (n = 21 474) or SGA (n = 2206); we then included a matched control cohort (n = 94 720). Cox regression was used to assess the epilepsy risk in preterm and SGA children. To determine the associated factors for epilepsy, the preterm and SGA infants were divided into six groups according to the common complications related to brain development and were separated into three subgroups based on birthweight (BW). RESULTS: The cumulative incidence of epilepsy was significantly higher in preterm or SGA children than in the control group. The overall incidence densities (per 1000 person-years) of epilepsy were: 0.37 in the control, 2.96 in the preterm, 2.90 in the SGA, 15.9 in the preterm with cerebral haemorrhage, 14.6 in the SGA with cerebral haemorrhage, 6.92 in the preterm with asphyxia, 3.82 in the SGA with asphyxia, 14.3 in the preterm with congenital brain anomalies, and 25.4 in the SGA with congenital brain anomalies cohorts. Infants with BW < 1000 g had a higher incidence of epilepsy than those with BW ≥2500 g. CONCLUSIONS: Preterm and SGA infants had an increased risk of epilepsy in childhood, and the incidence of epilepsy increased with decreasing BW. Several perinatal factors (e.g. intracranial haemorrhage, birth asphyxia and congenital brain anomalies) are associated with a higher incidence of later epilepsy.

Greater Protective Potent of s-Methyl Cysteine and Syringic Acid Combination for NGF-differentiated PC12 Cells against Kainic acid-induced Injury.

Objective: The effects of pre-treatments from s-methyl cysteine (SMC) alone, syringic acid (SA) alone and SMC plus SA against kainic acid (KA) induced injury in nerve growth factor (NGF) differentiated PC12 cells were investigated. Methods: NGF-differentiated PC12 cells were treated with 1 µM SMC, 1 µM SA or 0.5 µM SMC plus 0.5 µM SA for 2 days. Subsequently, cells were further treated by 150 µM KA. Results: KA suppressed Bcl-2 mRNA expression, enhanced Bax mRNA expression and casued cell death. SMC was greater than SA, and similar as SMC+SA in increasing Bcl-2 mRNA expression. SMC+SA led to greater increase in mitochondrial membrane potential and cell survival than SMC or SA alone. SMC+SA resulted in more reduction in reactive oxygen species and tumor necrosis factor-alpha generation, more increase in glutathione content and glutathione reductase activity than SMC or SA alone. KA up-regulated protein expression of nuclear factor kappa B (NF-κB) p65 and phosphorylated p38 (p-p38). SMC or SA pre-treatments alone limited protein expression of both factors. SMC+SA resulted in more suppression in NF-κB p65 and p-p38 expression. KA decreased glutamine level, increased glutamate level and stimulated calcium release. SMC pre-treatments alone reversed these alterations. SMC alone elevated glutamine synthetase (GS) activity and mRNA expression. SMC+SA led to greater GS activity and mRNA expression than SMC pre-treatments alone. Conclusion: These findings suggested that this combination, SMC+SA, might provide greater protective potent for neuronal cells.

Heterogeneous neurodevelopmental disorders in children with Kawasaki disease: what is new today?

BACKGROUND: Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children. METHODS: We retrospectively analyzed the data of children aged < 18 years with clinically diagnosed KD from January 1, 2005, to December 31, 2015. These patients were followed up to estimate the prevalence of epilepsy and associated NDDs in comparison with the prevalence in general pediatric population in Taiwan and worldwide. RESULTS: A total of 612 patients with an average age of 1.6 years were included. The prevalence of associated NDDs was 16.8% (n = 103/612) in the study group, which consisted of epilepsy, intellectual disability (ID), autism spectrum disorders, Tourette syndrome (TS), attention deficit hyperactivity disorder, (ADHD), and others. Moreover, children with KD had a higher prevalence of epilepsy and TS in both Taiwan and worldwide (epilepsy: 2.61% in the KD group vs 0.33% in Taiwan and 0.05-0.8% in worldwide, p < 0.05; TS: 2.77% in the KD group vs 0.56% in Taiwan and 0.3-1% in worldwide, p < 0.05). The prevalence of ID, ADHD, and developmental language disorders was not significantly different between our study patients and those in Taiwan or worldwide. CONCLUSIONS: Results revealed a higher prevalence rate of NDDs, especially epilepsy and TS, in Taiwanese children with KD than in the general pediatric population in Taiwan. However, these NDDs could be heterogeneous. Children diagnosed with KD were followed up because they had a higher risk of heterogeneous NDDs.

Whole exome sequencing in Dandy-Walker variant with intellectual disability reveals an activating CIP2A mutation as novel genetic cause.

Dandy-Walker malformation (DWM) has been reported to have heterogeneous causes, including mutations in genes of fibroblast growth factors and in genes in the sonic hedgehog (Shh) signaling pathway. Here, we identified an activating cancerous inhibitor of protein phosphatase 2A (CIP2A) p.D269V mutation, located at the predicted protein-protein interaction groove, as a novel genetic cause of Dandy-Walker variant (DWV). CIP2A has been reported as an oncoprotein promoting tumor survival via inhibition of protein phosphatase 2A (PP2A). However, the impact of human germline CIP2A mutation is unknown. We report a novel heterozygous CIP2A p.D269V mutation via whole exome sequencing in two siblings with DWV and severe intellectual disability who were born to non-consanguineous parents. Only the older brother developed a slow-growing sacral leiomyoma in his teens. The CIP2A p.D269V mutation is associated with increased PP2A, mTOR, and c-Myc protein levels in peripheral blood mononuclear cells (PBMCs). The PP2A phosphatase activity, however, was not suppressed. Deep sequencing revealed that the father carries 16% of somatic CIP2A p.D269V mutation, suggesting potential inheritance from the mosaic sperm populations. Our study is the first to describe a pathogenic CIP2A mutation in humans, which might disrupt neuronal development via enhancing mTOR and c-Myc protein expressions, shedding light in mechanisms of DWV pathogenesis.

Epileptic spasms in PPP1CB-associated Noonan-like syndrome: a case report with clinical and therapeutic implications.

BACKGROUND: Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2) is an extremely rare disease caused by a heterozygous mutation in the PPP1CB gene on chromosome 2p23. The syndrome causes not only numerous dysmorphic features but also hypotonia, developmental delay, and even intellectual disability. We report the first case of NSLH2 in Asia and the 16th in the world. Moreover, the first case of PPP1CB-related infantile spasms. The clinical and therapeutic significance is outlined in this paper. CASE PRESENTATION: We found a male infant presented with severe intractable epileptic spasms. Although certain clinical features of somatic dysmorphism were noted, numerous laboratory and neuroimaging studies failed to identify the cause. To determine the underlying etiology, whole-exome sequencing was conducted. We identified a de novo heterozygous mutation, NM_206876.1: c.548A > C (p.Glu183Ala), in the PPP1CB gene. His seizures were almost refractory to conventional antiepileptic drugs but relative seizure control was eventually achieved with a ketogenic diet. CONCLUSION: This result expands the clinical spectrum of NSLH2 and strengthens the association between the PPP1CB gene and epileptic seizures. Furthermore, we suggest that the ketogenic diet can offer seizure reduction in particular drug-resistant epilepsy syndromes. Additional studies are warranted to clarify the pathogenic mechanisms underlying this PPP1CB mutation in epileptic seizures.

Regression of Neonatal Cardiac Rhabdomyoma in Two Months Through Low-Dose Everolimus Therapy: A Report of Three Cases.

Cardiac rhabdomyoma (CR) is the most common cardiac tumor in newborns. Approximately 75% of cases are associated with tuberous sclerosis complex. Although these tumors usually spontaneously regress after 2 years of age, they can be life-threatening when they obstruct major cardiac inflow or outflow pathways. Everolimus is an inhibitor of the mammalian target of rapamycin, reducing its production of the proteins harmartin and tuberin. Everolimus has demonstrated a remarkable suppression effect in children with tuberous sclerosis complex at doses of 4.7-5.6 mg/M2/day and serum trough levels of 5-15 ng/mL. Since 2012, five case reports of neonates with CR have also reported the tumor-regressing effect of everolimus. However, the optimal dosage for neonates is still unknown. Over the past 2 years, we have deliberately used a low dose everolimus regimen (0.3-0.67 mg/M2/day) in three neonates with large CRs, in an effort to maintain serum trough levels at 3-7 ng/mL. In all three cases, the tumors regressed smoothly within 2 months. Regarding the drug's side effect of predisposing patients to infection, we observed that adenovirus pneumonia occurred in one case at 3 months of age, and chicken pox occurred in another case at 9 months of age; both recovered smoothly. Our three cases of neonatal CR demonstrate that a low-dose everolimus regimen is an effective treatment for tumor regression.

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study.

AIMS/HYPOTHESIS: Type 1 diabetes mellitus is a major public health problem of increasing global concern, with potential neurological complications. A possible association exists between type 1 diabetes and subsequent epilepsy. This study evaluated the relationship between type 1 diabetes and epilepsy in Taiwan. METHODS: Claims data from the Taiwan National Health Insurance Research Database were used to conduct retrospective cohort analyses. The study cohort contained 2568 patients with type 1 diabetes, each of whom was frequency-matched by sex, urbanisation of residence area and index year with ten patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. RESULTS: In patients with type 1 diabetes, the risk of developing epilepsy was significantly higher than that in patients without type 1 diabetes (p < 0.0001 for logrank test). After adjustment for potential confounders, the type 1 diabetes cohort was 2.84 times as likely to develop epilepsy than the control cohort was (HR 2.84 [95% CI 2.11, 3.83]). CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes are at an increased risk of developing epilepsy. Metabolic abnormalities of type 1 diabetes, such as hyperglycaemia and hypoglycaemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae. The causative factors between type 1 diabetes and the increased risk of epilepsy require further investigation.

Genetic association signal near NTN4 in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10(-4) ) remained significant after Bonferroni correction. Meta-analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10(-7) ). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case-control status (p = 0.042), suggesting that many of these variants are true TS risk alleles.

Deletion of exon 4 in the N-acetylgalactosamine-4-sulfatase gene in a Taiwanese patient with mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), one of the enzymes required for the degradation of dermatan sulfate (DS). Accumulation of DS in connective tissue causes growth failure, resulting in short stature. Here, we observed a 5-year-old girl who was the only one affected member of her family and who presented with an exaggerated, convex curvature of the back at the age of one year. Abnormal excretion of DS in the urine and extremely low leukocyte ARSB activity were noted. The patient was suspected to have MPS VI. Direct DNA sequencing indicated that there was no mutation in the coding region of ARSB. However, RT-PCR analysis of RNA prepared from blood samples indicated the deletion of the entire exon 4. Further analysis of the genomic DNA by quantitative PCR confirmed a homozygous deletion of exon 4, an unusual intragenic deletion in ARSB. The deletion led to a truncated protein that lacks most of the catalytic domain. The patient received recombinant human ARSB as enzyme replacement therapy (ERT) at an early stage (2 years), and responded positively in terms of skeletal development and other developmental milestones. The early identification of type VI MPS patients and subsequent treatment with ERT may be beneficial for the clinical outcome of MPS VI patients. In addition, detailed gene analysis may enhance the ability to provide genetic counseling to families of patients affected by MPS VI.

Attention-deficit-hyperactivity disorder increases risk of bone fracture: a population-based cohort study.

AIM: Attention-deficit-hyperactivity disorder (ADHD) is a disorder that is associated with accidental injuries. The aim of this study was to evaluate the relationship between ADHD and bone fracture in children. METHOD: The study cohort comprised 3640 children (2874 males, 766 females; mean age 8y 5mo, SD 3y) with ADHD (International Classification of Diseases, Ninth Revision) who were matched to children without ADHD at a ratio of 1:4 (n=14 560; 11 496 males, 3064 females; mean age 8y 5mo, SD 3y). A Cox proportional hazard regression analysis was conducted to estimate how ADHD affected the risk of bone fracture. RESULTS: The incidence of fracture among the ADHD cohort was 197.67 per 10,000 person-years, and was 1.3-fold greater than in the comparison cohort (147.54 per 10,000 person-years). The risk in children with ADHD was higher than that in children without ADHD (p value for log-rank test < 0.001). After adjusting for potential confounding factors, the ADHD cohort was 1.32 times more likely to have bone fracture accidents than the comparison cohort (hazard ratio, 1.32; 95% confidence interval 1.17-1.49). INTERPRETATION: Children with ADHD have a higher risk of experiencing bone fracture accidents than do children without ADHD.

Demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage in different types of corpus callosum disorders: a comparative study in children.

BACKGROUND: This study aimed to investigate the demographic and clinical characteristics, types of seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. METHODS: A total of 73 individuals were included in the study and divided into three groups based on the type of corpus callosum abnormality: hypoplasia (H), agenesis (A), and dysgenesis (D). Demographic data, including gender and preterm birth, as well as clinical characteristics such as seizure disorders, attention deficit hyperactivity disorder (ADHD), severe developmental delay/intellectual disability, and other brain malformations, were analyzed. The types of seizure disorders and antiepileptic drugs used were also examined. RESULTS: The H group had the highest number of participants (n = 47), followed by the A group (n = 11) and the D group (n = 15). The A group had the highest percentage of males and preterm births, while the D group had the highest percentage of seizure disorders, other brain malformations, and severe developmental delay/intellectual disability. The A group also had the highest percentage of ADHD. Focal seizures were observed in all three groups, with the highest proportion in the A group. Focal impaired awareness seizures (FIAS) were present in all groups, with the highest proportion in the D group. Generalized tonic-clonic seizures (GTCS) were observed in all groups, with the highest proportion in the H group. Different types of antiepileptic drugs were used among the groups, with variations in usage rates for each drug. CONCLUSION: This study provided insights into the demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. Significant differences were found between the groups, indicating the need for tailored management approaches. However, the study has limitations, including a small sample size and a cross-sectional design. Further research with larger sample sizes and longitudinal designs is warranted to validate these findings and explore the relationship between corpus callosum abnormality severity and clinical outcomes.

Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population. METHODS: GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1,007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed. RESULTS: Genome-wide significant locus, rs12313062 (p=1.43 × 10-8) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with DRAM1 and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption. CONCLUSIONS: This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with DRAM1. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low bone mineral density (BMD) (typically < -2.5 SD), cause a higher fracture risk and lead to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians. We investigated the genetic aspects of BMD in 86,716 individuals from the Taiwan Biobank and their causal links to health conditions within East Asians. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-ß. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with body mass index (BMI) and type 2 diabetes (T2D) in East Asians. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, HbA1c, and reduced T2D risk. Bidirectional Mendelian randomization (MR) analyses revealed that a higher BMI causally increases BMD in East Asians. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in East Asians, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

We investigated how genetics affect bone health and related conditions like diabetes and obesity in 86,716 East Asians. Previously, most studies focused on Caucasian populations, but our work helps to understand these issues in East Asians. Our findings show that stronger bones are linked to a lower chance of osteoporosis but a higher risk of obesity and type 2 diabetes. On the other hand, those with osteoporosis tend to have lower body weight and a decreased risk of diabetes, illustrating a complex relationship between bone health and body metabolism. Future research will focus on deeper genetic interactions and developing targeted interventions for bone health and related metabolic disorders in East Asians.

Association of poly(ADP-ribose) polymerase-1 polymorphism with Tourette syndrome.

Tourette syndrome (TS) is an etiologically heterogeneous disorder, the pathogenesis of which is incompletely understood. Poly(ADP-ribose) polymerase 1 (PARP1) is involved in regulation of developmental processes and cellular differentiation, in transcription regulation, in DNA repair, and in cell death. However, the relationship between TS and single nucleotide polymorphisms (SNPs) of PARP1 is unknown. Therefore, the aim of this experiment was to test the hypothesis that whether the PARP1 SNP, rs1805404 (c.243C>T, Asp81Asp), had an association with TS. A case-control experiment was designed to test this hypothesis. 123 TS children and 122 normal children were enrolled in this study. Polymerase chain reaction restriction fragment length polymorphism was used for the detection of the PARP1 SNP, rs1805404, in TS patients and normal children. The data showed that there is a significant difference in genotype distributions between these two groups. The CT genotype was a risk factor for TS with an odds ratio of 2.34 for the CT versus TT genotype (95% CI 1.16-4.74). The data also showed this SNP had an association with TS under recessive model (P = 0.0426), and TT genotype had a protective effect against TS with an odds ratio of 0.50 (95% CI 0.26-0.98). The findings of this study suggested that variants in the PARP1 gene might play a role in susceptibility to TS.

Association of tyrosyl-DNA phosphodiesterase 1 polymorphism with Tourette syndrome in Taiwanese patients.

BACKGROUND: Genetic, environmental, immunological, and hormonal factors contribute to the etiology of Tourette syndrome (TS). From the genetic standpoint, TS is a heterogeneous disorder. In our previous study, we found that a single nucleotide polymorphism (SNP) of x-ray repair cross-complementing group 1 (XRCC1), a DNA repair gene, was associated with TS. Previous studies also showed that tyrosyl-DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is unknown. Therefore, the aim of this study was to test the hypothesis that if the TDP1 SNP, rs28365054 (c.400G>A, Ala134Thr), was associated with TS or not. METHODS: A case-control study was designed to test the hypothesis. A total of 122 TS children and 106 normal children participated in the study. We used polymerase chain reaction to identify the SNP, rs28365054, of the TDP1 gene in the TS patients and the normal children. RESULTS: A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the TS patients and the control group. The AG genotype was a risk factor for TS with an odds ratio of 2.26 for the AG versus AA genotype (95% CI 1.08-4.72). CONCLUSION: The findings of this study suggested that variants in the TDP1 gene might play a role in TS susceptibility.

Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics.

Advances in disease-related gene discovery have led to tremendous innovations in the field of epilepsy genetics. Identification of genetic mutations that cause epileptic encephalopathies has opened new avenues for the development of targeted therapies. Clinical testing using extensive gene panels, exomes, and genomes is currently accessible and has resulted in higher rates of diagnosis and better comprehension of the disease mechanisms underlying the condition. Children with developmental disabilities have a higher risk of developing epilepsy. As our understanding of the mechanisms underlying encephalopathies and epilepsies improves, there may be greater potential to develop innovative therapies tailored to an individual's genotype. This article provides an overview of the significant progress in epilepsy genomics in recent years, with a focus on developmental and epileptic encephalopathies in children. The aim of this review is to enhance comprehension of the clinical utilization of genetic testing in this particular patient population. The development of effective and precise therapeutic strategies for epileptic encephalopathies may be facilitated by a comprehensive understanding of their molecular pathogenesis.