A5006135075- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Genetic Associations and Epidemiology
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Autism Spectrum Disorder Research
- BRCA gene mutations in cancer
- Prenatal Screening and Diagnostics
- Attention Deficit Hyperactivity Disorder
- Health, Environment, Cognitive Aging
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Epigenetics and DNA Methylation
- Advanced Neuroimaging Techniques and Applications
- Birth, Development, and Health
- Glioma Diagnosis and Treatment
- Psychiatric care and mental health services
- Child and Adolescent Psychosocial and Emotional Development
- Intracranial Aneurysms: Treatment and Complications
- Viral Infections and Immunology Research
- Adolescent and Pediatric Healthcare
- CNS Lymphoma Diagnosis and Treatment
- Child and Adolescent Health
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Microtubule and mitosis dynamics
- Mental Health and Patient Involvement
Cardiff University
2012-2024
Centre for Mental Health
2021
Mental Health Research Institute
2020
Wellcome Trust
2019
Medical Research Council
2016
University Hospital of Wales
2012
Swansea University
2012
University of Wales
2007
Genomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study consequences of middle and old age half a million well-phenotyped adults.
<h3>Importance</h3> At least 11 rare copy number variants (CNVs) have been shown to be major risk factors for schizophrenia (SZ). These CNVs also increase the other neurodevelopmental disorders, such as intellectual disability. It is possible that additional disability–associated SZ but not yet implicated in because of previous studies being underpowered. <h3>Objective</h3> To examine whether disability represent novel loci. <h3>Design, Setting, and Participants</h3> We used...
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects many individual CNVs in carriers without not yet fully understood, little is known about reciprocal changes pathogenic loci.AimsWe aimed to analyse effect CNV carrier status on performance measures occupational social outcomes unaffected individuals...
Psychotic experiences, such as hallucinations and delusions, are reported by approximately 5% to 10% of the general population, although only a small proportion develop psychotic disorders schizophrenia. Studying genetic causes experiences in its association with other disorders, may increase understanding their pathologic significance.
The role of large, rare copy number variants (CNVs) in neuropsychiatric disorders is well established, but their association with common psychiatric disorders, such as depression, remains unclear.To examine the a group 53 CNVs associated neurodevelopmental and burden risk depression.This case-control study used data from UK Biobank sample, which comprised 502 534 individuals living United Kingdom. Individuals autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity...
Copy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them associated with changes in weight, height, other traits. As most studies performed on children young people, these effects CNVs middle-aged older people are not well established. The UK Biobank recruited half a million adults who provided variety measurements. We called all from the Affymetrix microarrays selected set 54 implicated as pathogenic...
Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups also studied an attempt to identify changes that do not reflect reverse causation or treatment effects. However, no robust associations observed between neuroanatomical phenotypes and known genetic risk factors schizophrenia. We tested subcortical volume differences 49 unaffected participants carrying at least one of the 12 copy...
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, synaptic plasticity. These processes when perturbed thought contribute schizophrenia pathophysiology. A core feature is cognitive dysfunction. For genetic disorders where impairment more severe such as intellectual disability, there a disproportionally high number genes involved in the epigenetic...
Background The past decade has seen the development of services for adults presenting with symptoms autism spectrum disorder (ASD) in UK. Compared children, little is known about phenotypic and genetic characteristics these patients. Aims This e-cohort study aimed to examine a clinically sample diagnosed ASD by specialist services. Method Individuals as were recruited National Centre Mental Health completed self-report questionnaires, interviews provided DNA; 105 eligible individuals matched...
X-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by deletions spanning STS. Some medical comorbidities have been identified in XLI cases, but small samples relatively young patients has limited this. STS highly expressed subcortical brain structures, and males with female deletion carriers appear at increased risk developmental/mood disorders associated traits; neurocognitive basis these findings...
There is strong evidence that people born in winter and spring have a small increased risk of schizophrenia. As this 'season birth' effect underpins some the most influential hypotheses concerning potentially modifiable exposures, it important to exclude other possible explanations for phenomenon.Here we sought determine whether season birth reflects gene-environment confounding rather than pathogenic process indexing environmental exposure. We directly measured, 136 538 participants from UK...
Abstract The spectrum of non-motor symptoms in dystonia remains unclear. Using UK Biobank data, we analysed clinical phenotypic and genetic information the largest cohort reported to date. Case–control comparison matched control was undertaken identify domains (psychiatric, pain, sleep cognition) increased symptom burden dystonia. Whole exome data were used determine rate likely pathogenicity variants Mendelian inherited causing genes linked data. Within cohort, single-nucleotide...
Synaptosomal Associated Protein 25 kDa (SNAP25) has been implicated in the pathogenesis of schizophrenia by numerous neuropathological studies and genetic variation at SNAP25 reported to be associated with ADHD. Expression levels putative susceptibility gene DTNBP1 shown influence vitro. We undertook directed mutation screening UK schizophrenic cases followed direct association analysis all variants identified known exonic SNPs that showed evidence for (rs3746544 P = 0.004 OR 1.26, rs8636...
Copy number variations at the 15q11.2 BP1-BP2 locus are present in 0.5%-1.0% of population, and deletion is associated with several neurodevelopmental disorders. Previously, we showed a reciprocal effect copy variation on fractional anisotropy, widespread increases carriers. We aim to expand these findings using larger sample participants (N = 29,166) higher resolution imaging by examining implications for cognitive performance.
Deletions spanning the STS (steroid sulfatase) gene at Xp22.31 are associated with X-linked ichthyosis, corneal opacities, testicular maldescent, cardiac arrhythmia, and higher rates of developmental mood disorders/traits, possibly related to smaller volume some basal ganglia structures. The consequences duplication same genomic region have not been systematically assessed in large or adult samples, although evidence from case reports/series has indicated high phenotypes. We compared...
Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for will contribute to uncovering its underpinnings.To examine effect rare copy number variants (CNVs) associated schizophrenia cortical in sample unaffected participants from UK Biobank.We used regression analyses compare thickness and surface area (total across gyri) between 120 carriers CNVs 16 670 without any pathogenic CNV. A measure...
Anxiety and depression are common mental health disorders have a higher prevalence in females. They modestly heritable, share genetic liability with other psychiatric disorders, highly heterogeneous. There is evidence that to neurodevelopmental such as attention deficit hyperactivity disorder (ADHD) associated anxiety depression, particularly We investigated sex differences family history for risk burden (indexed by ADHD polygenic scores (PRS) rare copy number variants; CNVs) individuals...
Abstract Background Genomic copy number variants (CNVs) increase risk for early-onset neurodevelopmental disorders but their impact on medical outcomes in later life is poorly understood. The UK Biobank, with half a million well-phenotyped adults, presents an opportunity to study the consequences of CNV middle and old age. Methods We called 54 CNVs associated clinical phenotypes or genomic disorders, including reciprocal deletions duplications, all Biobank participants. used logistic...
ABSTRACT Background Pathogenic copy number variants (CNVs) increase risk for medical disorders, even among carriers free from neurodevelopmental disorders. The UK Biobank recruited half a million adults who provided samples biochemical and haematology tests which have recently been released. We wanted to assess how the presence of pathogenic CNVs affects these test results. Methods called all Affymetrix microarrays selected set 54 implicated as (including their reciprocal...