Building causal knowledge in behavior genetics DOI
James W. Madole, K. Paige Harden

Behavioral and Brain Sciences, Journal Year: 2022, Volume and Issue: 46

Published: May 5, 2022

Behavior genetics is a controversial science. For decades, scholars have sought to understand the role of heredity in human behavior and life-course outcomes. Recently, technological advances rapid expansion genomic databases facilitated discovery genes associated with phenotypes such as educational attainment substance use disorders. To maximize potential this flourishing science, minimize harms, careful analysis what it would mean for be causes needed. In paper, we advance framework identifying instances genetic causes, interpreting those causal relationships, applying them knowledge more generally social sciences. Central thinking about counterfactual reasoning, cornerstone statistics, medicine, philosophy. We argue that within-family effects represent product comparison same way average treatment (ATEs) from randomized controlled trials (RCTs). Both ATEs RCTs are shallow causes: They operate within intricate systems (non-unitary), produce heterogeneous across individuals (non-uniform), not mechanistically informative (non-explanatory). Despite these limitations, can used improve understanding etiology explore sources heterogeneity fade-out effects.

Language: Английский

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders DOI Open Access
Alexander S. Hatoum, Sarah M. C. Colbert, Emma C. Johnson

et al.

Nature Mental Health, Journal Year: 2023, Volume and Issue: 1(3), P. 210 - 223

Published: March 22, 2023

Language: Английский

Citations

130
The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research DOI
Roman Kotov, David C. Cicero, Christopher Conway

et al.

Psychological Medicine, Journal Year: 2022, Volume and Issue: 52(9), P. 1666 - 1678

Published: June 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.

Language: Английский

Citations

91
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals DOI Creative Commons
Hang Zhou, Rachel L. Kember, Joseph D. Deak

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(12), P. 3184 - 3192

Published: Dec. 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.

Language: Английский

Citations

82
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction DOI
Rachel L. Kember,

Rachel Vickers‐Smith,

Heng Xu

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(10), P. 1279 - 1287

Published: Sept. 28, 2022

Language: Английский

Citations

72
CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice DOI Creative Commons
Sandra Sanchez‐Roige,

Mariela Jennings,

Hayley H. A. Thorpe

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 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.

Language: Английский

Citations

44
Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes DOI
Sylvanus Toikumo,

Mariela Jennings,

Benjamin K. Pham

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(6), P. 1177 - 1193

Published: April 17, 2024

Language: Английский

Citations

18
Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability DOI
I‐Tzu Hung, Essi Viding, Argyris Stringaris

et al.

Journal of the American Academy of Child & Adolescent Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

3
Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with an alcohol use disorder DOI
Peter B. Barr, Zoë Neale,

Chris Chatzinakos

et al.

Complex Psychiatry, Journal Year: 2025, Volume and Issue: 11(1), P. 1 - 11

Published: Feb. 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.

Language: Английский

Citations

2
The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates DOI Open Access
Alexander S. Hatoum, Emma C. Johnson, Sarah M. C. Colbert

et al.

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(10), P. 1739 - 1745

Published: Nov. 8, 2021

Language: Английский

Citations

86
Polygenic scores: prediction versus explanation DOI Creative Commons
Robert Plomin, Sophie von Stumm

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 49 - 52

Published: Oct. 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.

Language: Английский

Citations

65