Sophie E. Legge
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View article: Near, far, wherever you are: Phenotype-related variation in pharmacogenomic effect sizes across the psychiatric drug literature
Near, far, wherever you are: Phenotype-related variation in pharmacogenomic effect sizes across the psychiatric drug literature Open
Background Pharmacogenomics is viewed as one route to minimising inter-individual variability in drug response. However, uptake in psychiatry is slower than in other medical fields, so assessing evidence for psychiatric genotype-drug pairs…
View article: Associations between psychotic experience dimensions and polygenic liability to schizophrenia in a longitudinal birth cohort
Associations between psychotic experience dimensions and polygenic liability to schizophrenia in a longitudinal birth cohort Open
Background Some psychotic experiences in the general population show associations with higher schizophrenia and other mental health-related polygenic risk scores (PRSs), but studies have not usually included interviewer-rated positive, neg…
View article: Effects of Shared and Nonshared Schizophrenia and Bipolar Disorder Alleles on Cognition and Educational Attainment in the UK Biobank
Effects of Shared and Nonshared Schizophrenia and Bipolar Disorder Alleles on Cognition and Educational Attainment in the UK Biobank Open
View article: The relationship between schizophrenia polygenic scores, blood-based proteins and psychosis diagnosis in the UK Biobank
The relationship between schizophrenia polygenic scores, blood-based proteins and psychosis diagnosis in the UK Biobank Open
Despite notable progress in psychiatric genomics, there are no validated blood-based biomarkers for psychosis. Previous studies have failed to establish a link between schizophrenia polygenic scores (PGS) and blood protein levels. We aimed…
View article: The Role of <scp>SLC39A8</scp> .p.( <scp>Ala391Thr</scp> ) in Schizophrenia Symptom Severity and Cognitive Ability: Cross‐Sectional Studies of Schizophrenia and the General <scp>UK</scp> Population
The Role of <span>SLC39A8</span> .p.( <span>Ala391Thr</span> ) in Schizophrenia Symptom Severity and Cognitive Ability: Cross‐Sectional Studies of Schizophrenia and the General <span>UK</span> Population Open
The missense SNP NC_000004.12:g.102267552C>T (also known as SLC39A8.p.(Ala391Thr), rs13107325) in SLC39A8 encodes a zinc transporter. This SNP has been linked to schizophrenia and is the likely causal variant for one of the genome‐wide ass…
View article: Antipsychotic and pharmacogenomic effects on cross-sectional symptom severity and cognitive ability in schizophrenia
Antipsychotic and pharmacogenomic effects on cross-sectional symptom severity and cognitive ability in schizophrenia Open
View article: The relationship between shared and differentiating genetic liability for schizophrenia and bipolar disorder and cognition and educational attainment in the UK Biobank
The relationship between shared and differentiating genetic liability for schizophrenia and bipolar disorder and cognition and educational attainment in the UK Biobank Open
Importance Further understanding how genetic liabilities to schizophrenia (SZ) and bipolar disorder (BD) are related to cognition and educational attainment (EA) indicates important differences between these conditions that are relevant to…
View article: Medication and pharmacogenomic effects on cross-sectional symptom severity and cognitive ability in schizophrenia
Medication and pharmacogenomic effects on cross-sectional symptom severity and cognitive ability in schizophrenia Open
Background People with schizophrenia differ in the type and severity of symptoms experienced, as well as their response to medication. A better understanding of the factors that influence this heterogeneity is necessary for the development…
View article: Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples
Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples Open
Background Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investi…
View article: Assessing the validity of a self-reported clinical diagnosis of schizophrenia
Assessing the validity of a self-reported clinical diagnosis of schizophrenia Open
View article: SLC39A8.p.(Ala391Thr) is associated with poorer cognitive ability: a cross-sectional study of schizophrenia and the general UK population
SLC39A8.p.(Ala391Thr) is associated with poorer cognitive ability: a cross-sectional study of schizophrenia and the general UK population Open
The missense SNP NC_000004.12:g.102267552C>T (SLC39A8.p.(Ala391Thr), rs13107325) in SLC39A8, which encodes a zinc transporter, has been linked to schizophrenia and is the likely causal variant for one of the genome-wide association loci as…
View article: Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause
Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause Open
Although the relationship between perimenopause and changes in mood has been well established, knowledge of risk of a broad spectrum of psychiatric disorders associated with reproductive aging is limited. Here we investigate whether the pe…
View article: Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia
Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia Open
View article: Understanding clozapine-related blood dyscrasias. Developments, genetics, ethnicity and disparity: it's a CIN
Understanding clozapine-related blood dyscrasias. Developments, genetics, ethnicity and disparity: it's a CIN Open
Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of thi…
View article: Common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure
Common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure Open
Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for sc…
View article: Genetic and Phenotypic Features of Schizophrenia in the UK Biobank
Genetic and Phenotypic Features of Schizophrenia in the UK Biobank Open
Importance Large-scale biobanks provide important opportunities for mental health research, but selection biases raise questions regarding the comparability of individuals with those in clinical research settings. Objective To compare the …
View article: Associations between symptoms, cognition, and pharmacogenomics in a cross-sectional sample of people with schizophrenia treated with antipsychotics
Associations between symptoms, cognition, and pharmacogenomics in a cross-sectional sample of people with schizophrenia treated with antipsychotics Open
View article: First occurrences of psychiatric disorders during the perimenopause
First occurrences of psychiatric disorders during the perimenopause Open
View article: Severe psychiatric disorders are associated with increased risk of dementia
Severe psychiatric disorders are associated with increased risk of dementia Open
Background Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited eviden…
View article: Assessing the validity of a self-reported clinical diagnosis of schizophrenia
Assessing the validity of a self-reported clinical diagnosis of schizophrenia Open
Background Diagnoses in psychiatric research can be derived from various sources. This study assesses the validity of a self-reported clinical diagnosis of schizophrenia. Methods The study included 3,029 clinically ascertained participants…
View article: Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count
Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count Open
View article: Genomic findings in schizophrenia and their implications
Genomic findings in schizophrenia and their implications Open
View article: Mediation and Longitudinal Analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count
Mediation and Longitudinal Analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count Open
Clozapine is effective at reducing symptoms of treatment-resistant schizophrenia, but it can also induce several adverse outcomes including neutropenia and agranulocytosis. We used linear mixed-effect models and structural equation modelli…
View article: Early neutrophil trajectory following clozapine may predict clozapine response – Results from an observational study using electronic health records
Early neutrophil trajectory following clozapine may predict clozapine response – Results from an observational study using electronic health records Open
Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficac…
View article: Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions
Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions Open
View article: Common risk alleles for schizophrenia within the Major Histocompatibility Complex predict white matter microstructure
Common risk alleles for schizophrenia within the Major Histocompatibility Complex predict white matter microstructure Open
Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for sc…
View article: Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance
Copy Number Variants Increasing Risk for Schizophrenia: Shared and Distinct Effects on Brain Morphometry and Cognitive Performance Open
View article: Ultrarare Coding Variants and Cognitive Function in Schizophrenia
Ultrarare Coding Variants and Cognitive Function in Schizophrenia Open
Importance Impaired cognitive function in schizophrenia is associated with poor functional outcomes, but the role of rare coding variants is unclear. Objective To determine whether ultrarare constrained variants (URCVs) are associated with…
View article: Genomic Stratification of Clozapine Prescription Patterns Using Schizophrenia Polygenic Scores
Genomic Stratification of Clozapine Prescription Patterns Using Schizophrenia Polygenic Scores Open
The schizophrenia PRS was associated with the highest clozapine dose prescribed for an individual in records from 3 independent samples, suggesting that the genetic liability for schizophrenia might index factors associated with therapeuti…
View article: Schizophrenia Polygenic Risk and Experiences of Childhood Adversity: A Systematic Review and Meta-analysis
Schizophrenia Polygenic Risk and Experiences of Childhood Adversity: A Systematic Review and Meta-analysis Open
Background and Hypothesis Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental risk factors for schizophrenia, but it is unc…