Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders

Nature Mental Health, Год журнала: 2023, Номер 1(3), С. 210 - 223

Опубликована: Март 22, 2023

Язык: Английский

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The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research

Psychological Medicine, Год журнала: 2022, Номер 52(9), С. 1666 - 1678

Опубликована: Июнь 2, 2022

Abstract The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out the quantitative approach to psychiatric nosology. This identifies psychopathology constructs based on patterns co-variation among signs and symptoms. initial HiTOP model, which was published in 2017, is a large literature that spans decades research. living model undergoes revision as new data become available. Here we discuss advantages practical considerations using this system practice We especially highlight limitations ongoing efforts address them. describe differences similarities between existing diagnostic systems. Next, review types evidence informed development HiTOP, including populations it been studied its validity. paper also describes how can facilitate research genetic environmental causes well search for neurobiologic mechanisms novel treatments. Furthermore, consider implications public health programs prevention mental disorders. clinical utility illustrate application HiTOP. Importantly, measures practices are already used widely settings. offers way organize formalize these techniques. contribute progress psychiatry complement traditional nosologies. Moreover, seeks linkages phenotypes biological processes, may enable construction encompasses both biomarkers precise description.

Язык: Английский

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Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals

Nature Medicine, Год журнала: 2023, Номер 29(12), С. 3184 - 3192

Опубликована: Дек. 1, 2023

Abstract Problematic alcohol use (PAU), a trait that combines disorder and alcohol-related problems assessed with questionnaire, is leading cause of death morbidity worldwide. Here we conducted large cross-ancestry meta-analysis PAU in 1,079,947 individuals (European, N = 903,147; African, 122,571; Latin American, 38,962; East Asian, 13,551; South 1,716 ancestries). We observed high degree cross-ancestral similarity the genetic architecture identified 110 independent risk variants within- analyses. Cross-ancestry fine mapping improved identification likely causal variants. Prioritizing genes through gene expression chromatin interaction brain tissues multiple associated PAU. existing medications for potential pharmacological studies by computational drug repurposing analysis. polygenic scores showed better performance association samples than single-ancestry scores. Genetic correlations between other traits were ancestries, substance having highest correlations. This study advances our knowledge etiology PAU, these findings may bring possible clinical applicability genetics insights—together neuroscience, biology data science—closer.

Язык: Английский

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Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction

Nature Neuroscience, Год журнала: 2022, Номер 25(10), С. 1279 - 1287

Опубликована: Сен. 28, 2022

Язык: Английский

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CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Май 12, 2023

Abstract Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency act prematurely and associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) eight impulsive personality traits from Barratt Impulsiveness Scale short UPPS-P Impulsive Personality ( N = 123,509–133,517 23andMe research participants European ancestry), measure Drug Experimentation 130,684). Because these GWAS implicated gene CADM2 , we next single-SNP phenome-wide (PheWAS) several variants in multi-ancestral cohort 3,229,317, European; 579,623, Latin American; 199,663, African American). Finally, produced Cadm2 mutant mice used them perform Mouse-PheWAS (“MouseWAS”) by testing battery relevant behavioral tasks. In humans, showed modest chip-heritability (~6–11%), moderate genetic correlations r g 0.20–0.50) other traits, various psychiatric medical traits. identified significant associations proximal genes such as TCF4 PTPRF also nominal DRD2 CRHR1 . PheWAS for 378 participants, 47 American replicating risky behaviors, cognition BMI, revealing novel allergies, anxiety, irritable bowel syndrome, migraine. Our MouseWAS recapitulated some found impulsivity, cognition, BMI. results further delineate role impulsivity numerous somatic across ancestries species.

Язык: Английский

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Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes

Nature Human Behaviour, Год журнала: 2024, Номер 8(6), С. 1177 - 1193

Опубликована: Апрель 17, 2024

Язык: Английский

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Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability

Journal of the American Academy of Child & Adolescent Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with an alcohol use disorder

Complex Psychiatry, Год журнала: 2025, Номер 11(1), С. 1 - 11

Опубликована: Фев. 13, 2025

Introduction: Research has identified multiple risk factors associated with suicide attempt (SA) among individuals psychiatric illness. However, there is limited research those an alcohol use disorder (AUD), despite their disproportionately higher rates of SA. Methods: We examined lifetime SA in 4,068 AUD from the Collaborative Study on Genetics Alcoholism (23% SA; 53% female; mean age: 38). explored for across other clinical conditions ascertained a interview, polygenic scores comorbid problems, and neurocognitive functioning. Results: Participants who attempted had greater trauma exposure, major depressive disorder, post-traumatic stress substance disorders (SUDs), suicidal ideation. Polygenic SA, depression, PTSD were increased odds reporting (ORs = 1.22–1.44). reported also decreased right hemispheric frontal-parietal theta interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to did not, but differences small. Conclusions: Overall, report experience levels trauma, have more severe comorbidities, carry problems. Our results demonstrate need further investigate SAs presence SUDs.

Язык: Английский

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The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

Neuropsychopharmacology, Год журнала: 2021, Номер 47(10), С. 1739 - 1745

Опубликована: Ноя. 8, 2021

Язык: Английский

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Polygenic scores: prediction versus explanation

Molecular Psychiatry, Год журнала: 2021, Номер 27(1), С. 49 - 52

Опубликована: Окт. 22, 2021

During the past decade, polygenic scores have become a fast-growing area of research in behavioural sciences. The ability to directly assess people's genetic propensities has transformed by making it possible add predictors traits any study. value sciences rests on using inherited DNA differences predict, from birth, common disorders and complex unrelated individuals population. This predictive power does not require knowing anything about processes that lie between genes behaviour. It also mandate disentangling extent which prediction is due assortative mating, genotype-environment correlation, or even population stratification. Although bottom-up explanation brain behaviour will remain long-term goal sciences, worthy achievement because immediate practical utility for identifying at risk necessary first step towards explanation. A high priority must be increase able use them as an early warning system prevent problems.

Язык: Английский

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