Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Risk and Consequences of Child Abuse in Attention Deficit Hyperactivity Disorder

Awareness about child physical and emotional abuse and ndash;as well as sexual abuse- is increasing day by day. It is stated that the physical or emotional harm given to a child can result in serious psychological problems both in short and long terms. In addition to this, it is known that, the traditional discipline styles, especially applied in developing countries, can be physically and emotionally harmful and sometimes abusive. The stress level of the parent determines the parent's choice of discipline style and psychopathologies such as attention deficit hyperactivity disorder seem to be riskfull for physical and emotional abuse because they increase the stress level of parents. This paper will review the literature related to the probability of exposure to physically or emotionally abusive discipline styles for children with attention deficit hyperactivity disorder and also the literarture related to the consequences of these abusive discipline styles on these children. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2): 166-177

A Qualitative Study on Corporal Punishment And Emotionally Abusive Disciplinary Practices Among Mothers of Children With Adhd

OBJECTIVES: The present study aimed to investigate actual disciplinary behaviours of Turkish mothers' in the context of relational environment and to investigate ADHD as a risk factor on abusive disciplinary practices. METHODS: Totally 120 children (children with ADHD; study group and healthy controls; control group) - and their mothers were interviewed with this aim. The interviews were qualitatively coded and analysed. T-test and Odds ratio were used for descriptive statistics with the aim of supporting the qualitative results. RESULTS: According to the results of the study, emotionally abusive disciplinary behaviours (81% of all mothers 58% of all children) and corporal punishment (76% of all mothers and 65% of all children) were commonly used as a disciplinary method. Nevertheless, children with ADHD was shown to be at higher risk for both abusive disciplinary practices. The present study has also shown that children with ADHD and their mothers shared less positive activities compared to the control group. In addition to this, emotionally abusive disciplinary practices were found to be at least as hurtful as corporal punishment. CONCLUSIONS: To our knowledge, the present study was the first one investigating Turkish mothers' actual abusive disciplinary acts together with the relational environment between them and their children (including their relationship, positive sharing, problematic issues) by gathering information from both mothers and children of both study and control groups and then comparing these groups in terms of all these aspects. Qualitative nature of the study gave the opportunity of determining the actual disciplinary methods and the actual relational risk factors rather than attitudes and questionnaire scores about mother-child relationship. Therefore, it can be suggested that the results of the study provide important information about the abusive disciplinary behaviours of Turkish mothers and also provide the opportunity of predicting risk factors - keeping cultural context in mind - of these behaviours.WoSScopu

The utility of dual-energy X-ray absorptiometry, calcaneal quantitative ultrasound, and fracture risk indices (FRAX® and Osteoporosis Risk Assessment Instrument) for the identification of women with distal forearm or hip fractures: A pilot study

Purpose: Dual-energy X-ray absorptiometry (DXA) is considered the gold standard in predicting osteoporotic fractures. Calcaneal quantitative ultrasound (QUS) variables are also known to predict fractures. Fracture risk assessment tools may also guide us for the detection of individuals at high risk for fractures. The aim of this case-control study was to evaluate the utility of DXA bone mineral density (BMD), calcaneal QUS parameters, FRAX (R) (Fracture Risk Assessment Tool), and Osteoporosis Risk Assessment Instrument (ORAI) for the discrimination of women with distal forearm or hip fractures. Materials and methods: This case-control study included 20 women with a distal forearm fracture and 18 women with a hip fracture as cases and 76 age-matched women served as controls. BMD at the spine, proximal femur, and radius was measured using DXA and acoustic parameters of bone were obtained using a calcaneal QUS device. FRAX (R) 10-year probability of fracture and ORAI scores were also calculated in all participants. Receiver operating characteristic (ROC) analysis was used to assess fracture discriminatory power of all the tools. Results: While all DXA BMD, and QUS variables and FRAX (R) fracture probabilities demonstrated significant areas under the ROC curves for the discrimination of hip-fractured women and those without, only 33% radius BMD, broadband ultrasound attenuation (BUA), and FRAX (R) major osteoporotic fracture probability calculated without BMD showed significant discriminatory power for distal forearm fractures. Conclusions: It can be concluded that QUS variables, particularly BUA, and FRAX (R) major osteoporotic fracture probability without BMD are good candidates for the identification of both hip and distal forearm fractures

Cognitive And Behavioral Impairment In Mild Hyperphenylalaninemia

As elevated phenylalanine (Phe) is detrimental to brain functions, determining a safe upper limit of blood Phe is important for initiation of treatment plans and setting Phe targets in hyperphenlalaninemic patients. It is accepted that Phe levels below 360 mu mol/L does not impair brain function and hence does not require treatment. Therefore, we aimed to compare cognitive functions and attention-related problems among healthy children and untreated patients with hyperphenylalaninemia (HPA). This study included 41 hyperphenylalaninemic patients ("all HPA group") aged 6-16 years with untreated blood Phe between 240 and 600 mu mol/L and 29 healthy controls. "All HPA group" was further divided into 2 subgroups according to their lifetime median blood Phe levels as "Phe 360-600 mu mol/L" and "Phe 240-360 mu mol/L" groups. Wechsler Intelligence Scale for Children-IV (WISC-IV), Conners' Continuous Performance Test (CPT), Strength and Difficulties Questionnaire (SDQ) and Schedule for Affective Disorders and Schizophrenia for School-Age Children: Present and Lifetime Version (K-SADS-PL) were performed as a comprehensive neurocognitive, attention and behavioral assessment. The study illustrated that "all HPA" patients had significantly lower scores on all WISC-IV indexes compared to controls, except for Working Memory. Both "Phe 360-600 mu mol/L" and "Phe 240-360 mu mol/L" subgroups had lower Full Scale intelligence quotient (IQ) and Verbal Comprehension scores compared to controls. "All HPA" patients also had longer reaction times and more peer problems than controls, indicating attention deficits and behavioral problems. Since the results demonstrated that children with untreated Phe levels between 240-360 mu mol/L are at higher risk for cognitive and attention-related problems, lowering the "safe" upper Phe level should be considered.WoSScopu