A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex

Nature Genetics, Год журнала: 2022, Номер 54(9), С. 1284 - 1292

Опубликована: Июнь 2, 2022

Язык: Английский

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The contribution of copy number variants to psychiatric symptoms and cognitive ability

Molecular Psychiatry, Год журнала: 2023, Номер 28(4), С. 1480 - 1493

Опубликована: Фев. 3, 2023

Язык: Английский

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Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy

Nature Genetics, Год журнала: 2024, Номер 56(4), С. 585 - 594

Опубликована: Март 29, 2024

Язык: Английский

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Mental health challenges faced by autistic people

Nature Human Behaviour, Год журнала: 2023, Номер 7(10), С. 1620 - 1637

Опубликована: Окт. 20, 2023

Язык: Английский

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A genetics-first approach to understanding autism and schizophrenia spectrum disorders: the 22q11.2 deletion syndrome

Molecular Psychiatry, Год журнала: 2022, Номер 28(1), С. 341 - 353

Опубликована: Окт. 3, 2022

Recently, increasing numbers of rare pathogenic genetic variants have been identified that are associated with variably elevated risks a range neurodevelopmental outcomes, notably including Autism Spectrum Disorders (ASD), Schizophrenia (SSD), and Intellectual Disability (ID). This review is organized along three main questions: First, how can we unify the exclusively descriptive basis our current psychiatric diagnostic classification system recognition an identifiable, highly penetrant risk factor in proportion patients ASD or SSD? Second, what be learned from studies individuals SSD who share common basis? And third, accounts for observed variable penetrance pleiotropy neuropsychiatric phenotypes same variant? In this review, focus on findings clinical preclinical 22q11.2 deletion syndrome (22q11DS). particular variant not only one most among list known variants, but also benefits relatively long research history. Consequently, 22q11DS appealing model as it allows us to: (1) elucidate specific genotype-phenotype associations, (2) prospectively study behaviorally defined classifications, such SSD, context known, well-characterized basis, (3) mechanisms underpinning pleiotropy, phenomena far-reaching ramifications practice. We discuss animal vitro relate to observations human help factors, genetic, environmental, stochastic, impact expression 22q11DS, may inform underlying general population. conclude priorities field, which pave way novel therapeutics.

Язык: Английский

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Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies

Molecular Psychiatry, Год журнала: 2023, Номер 28(12), С. 4943 - 4953

Опубликована: Июль 4, 2023

Язык: Английский

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Gene copy number variation and pediatric mental health/neurodevelopment in a general population

Human Molecular Genetics, Год журнала: 2023, Номер 32(15), С. 2411 - 2421

Опубликована: Май 8, 2023

Abstract We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health cognition a community sample 7100 unrelated children youth European or East Asian ancestry (Spit for Science). Clinically significant susceptibility CNVs were present 3.9% participants associated with elevated scores on continuous measure attention-deficit/hyperactivity disorder (ADHD) (P = 5.0 × 10−3), longer response inhibition (a cognitive deficit found several neurodevelopmental disorders; P 1.0 10−2) increased prevalence diagnoses 1.9 10−6, odds ratio: 3.09), specifically ADHD, autism spectrum anxiety learning problems/learning (P’s < 0.01). There was an burden rare deletions gene-sets related to brain function expression more ADHD traits. With current crisis, our data established baseline delineating genetic contributors pediatric-onset conditions.

Язык: Английский

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Impact of Copy Number Variants and Polygenic Risk Scores on Psychopathology in the UK Biobank

Biological Psychiatry, Год журнала: 2023, Номер 94(7), С. 591 - 600

Опубликована: Фев. 9, 2023

Язык: Английский

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Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Nature Human Behaviour, Год журнала: 2023, Номер 7(6), С. 1001 - 1017

Опубликована: Март 2, 2023

Язык: Английский

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Consensus reporting guidelines to address gaps in descriptions of ultra-rare genetic conditions

npj Genomic Medicine, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 6, 2024

Abstract Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment novel conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians families is unclear. We identified reports published from 2017 2021 10 genetics journals Mendelian disorders. adjudicated the quality detail via 46 questions pertaining six priority domains: (I) Development, cognition, mental health; (II) Feeding growth; (III) Medication use treatment history; (IV) Pain, sleep, life; (V) Adulthood; (VI) Epilepsy. For subset articles, all subsequent follow-up case descriptions were assessed similar manner. A modified Delphi approach was used develop consensus reporting guidelines, with input content experts across four countries. In total, 200 3243 screened publications met inclusion criteria. Relevant phenotypic details each 6 domains rated superficial or deficient >87% papers. example, less than 10% provided regarding neuropsychiatric diagnoses “behavioural issues”, about type/nature feeding problems. Follow-up ( n = 95) rarely contributed this additional data. summary, information relevant clinical management, counselling, stated patients lacking many newly described diseases. PHELIX (PHEnotype LIsting fiX) guideline checklists developed improve genomic era.

Язык: Английский

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