The translation of psychiatric genetic findings to the clinic.

Mental health and neurodevelopmental disorders are highly heritable and can affect morbidity and mortality. A large, growing body of evidence has implicated both common and rare variation in the risk of these disorders. Testing for rare variants, such as copy number variants, has been available in clinical practice for some time in the context of developmental disorders.

Clinical and genotypic analysis in determining dystonia non-motor phenotypic heterogeneity: a UK Biobank study.

The spectrum of non-motor symptoms in dystonia remains unclear. Using UK Biobank data, we analysed clinical phenotypic and genetic information in the largest dystonia cohort reported to date. Case-control comparison of dystonia and matched control cohort was undertaken to identify domains (psychiatric, pain, sleep and cognition) of increased symptom burden in dystonia.

Analysis of Diffusion Tensor Imaging Data From the UK Biobank Confirms Dosage Effect of 15q11.2 Copy Number Variation on White Matter and Shows Association With Cognition.

Background: Copy number variations at the 15q11.2 BP1-BP2 locus are present in 0.5%-1.

Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.

Background: Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims: To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records.

Effects of genomic copy number variants penetrant for schizophrenia on cortical thickness and surface area in healthy individuals: analysis of the UK Biobank.

Background: Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.

Aims: To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.

Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank.

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 and mood disorders/traits, possibly related to the smaller volume of some basal ganglia structures. The consequences of duplication of the same genomic region have not been systematically assessed in large or adult samples, although evidence from case reports/series has indicated high rates of developmental phenotypes.

Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank.

Background: X-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by X-linked deletions spanning . Some medical comorbidities have been identified in XLI cases, but small samples of relatively young patients has limited this. is highly expressed in subcortical brain structures, and males with XLI and female deletion carriers appear at increased risk of developmental/mood disorders and associated traits; the neurocognitive basis of these findings has not been examined.

Association of Genetic Liability to Psychotic Experiences With Neuropsychotic Disorders and Traits.

Importance: 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 such as schizophrenia. Studying the genetic causes of psychotic experiences in the general population, and its association with the genetic causes of other disorders, may increase the understanding of their pathologic significance.

Objectives: To determine whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits and to identify genetic loci associated with psychotic experiences.

Association of Rare Copy Number Variants With Risk of Depression.

Importance: 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.

Objective: To examine the association of a group of 53 CNVs associated with neurodevelopmental disorders and burden of rare CNVs with risk of depression.

Design, Setting, And Participants: This case-control study used data from the UK Biobank study sample, which comprised 502 534 individuals living in the United Kingdom.

Autism spectrum disorder diagnosis in adults: phenotype and genotype findings from a clinically derived cohort.

Background: The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients.

Aims: This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services.

Cognitive performance and functional outcomes of carriers of pathogenic copy number variants: analysis of the UK Biobank.

Background: Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.AimsWe aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank.

Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia.

Effects of pathogenic CNVs on physical traits in participants of the UK Biobank.

Background: Copy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them have been associated with changes in weight, height, and other physical traits. As most studies have been performed on children and young people, these effects of CNVs in middle-aged and older people are not well established.

Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank.

Background: 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 the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.

Methods: We analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications.

Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects.

Background: The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population. We aimed to examine the effect of neurodevelopmental copy number variants (CNVs) on the cognitive performance of participants.

Methods: We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals.

A neurological presentation of intravascular B-cell lymphoma.

Intravascular B-cell lymphoma is a rare, aggressive subtype of diffuse large B-cell lymphoma that presents insidiously with symptoms relating to organ involvement. We present the case of a male in his late 40s who presented with fluctuating neurological symptoms including episodes of altered upper-limb sensation, seizures and psychotic phenomena. These symptoms and signs were associated with fleeting brain lesions on neuroimaging.