Impulsivity facets and substance use involvement: insights from genomic structural equation modeling

Psychological Medicine, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Abstract Background Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of involvement remains unclear. Methods We used genomic structural equation modeling genome-wide association studies ( N = 79,729–903,147) to examine latent genetic architecture nine traits seven (SU) SUD traits. Results found that SU factors were strongly genetically inter-correlated r G =0.77) their associations differed. Lack premeditation, negative positive urgency equally positively correlated both =.0.30–0.50) 0.38–0.46) factors; sensation seeking was more factor =0.27 versus =0.10); delay discounting =0.31 =0.21); lack perseverance only weakly =0.10). After controlling for correlation SU/SUD, we premeditation independently (β=0.42) (β=0.21); (β=0.48, β=0.33, respectively); (β=0.33, β=0.36, respectively). Conclusions Our findings show specific confer risk involvement, potential implications SUDs prevention treatment.

Language: Английский

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Trans-ancestry Genome-Wide Analyses in UK Biobank Yield Novel Risk Loci for Major Depression

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Most genome-wide association studies (GWASs) of depression focus on broad, heterogeneous outcomes, limiting the discovery genomic risk loci specific to major depressive disorder (MDD). Previous UK Biobank (UKB) had limited ability pinpoint MDD-associated due a smaller sample with strictly defined MDD outcomes and further exclusion many participants based ancestry or relatedness, significantly underutilizing this resource's potential for elucidating genetic architecture MDD. Here, we present novel insights into by fully utilizing existing UKB data through (1) trans-ancestry GWAS pipeline using two complementary approaches controlling population structure relatedness (2) an increased symptom-level across mental health assessments. We identified strict among 211,535 participants, representing 38% increase in eligible from prior only one assessment. Ancestrally inclusive analyses yielded 61 phenotypes, compared 47 restricted genetically similar European ancestry. Fourteen these loci, including five novel, were associated whereas locus has been previously reported UKB. predicted gene expression levels showed little overlap broad depression, indicating higher specificity. Notably, polygenic scores results diagnoses groups All Us Research Program, highlighting shared populations. While analyses, which included non-European number ancestry-specific was limited, underscoring need larger, globally representative Importantly, beyond results, our will facilitate other traits disorders, helping improve statistical power, representation, generalizability studies.

Language: Английский

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Associations between air pollution and surrounding greenness with internalizing and externalizing behaviors among schoolchildren

Child and Adolescent Mental Health, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Air pollution and greenness are emerging as modifiable risk protective factors, respectively, in child psychopathology. However, research shows inconsistencies. Here, we examined associations between air surrounding with internalizing externalizing behaviors. In addition, the potential modifying role of genetic susceptibility for these traits socioeconomic status (SES) was explored. This population-based study included 4485 schoolchildren aged 5-18 years from Spain. Internalizing behaviors were assessed using Child Behavior Checklist (CBCL). Average (NO2, PM2.5, PM10, PMcoarse, PM2.5 absorbance) (NDVI within 100-m, 300-m, 500-m buffers) school exposure estimated 12 months before outcome assessment. Genetic liability by computing polygenic scores (PRS) SES calculated Hollingshead Four-Factor Index. Associations analyzed negative binomial mixed-effects models. Although no survived multiple testing, found that increases 5.48 μg/m3 PM10 2.93 PMcoarse associated a 6% (Mean Ratio (MR) = 1.06; 95% CI: 1.01-1.12) 4% (MR 1.04; 1.00-1.09) increase behavior scores. A 0.1 NDVI 100-m buffer decrease 0.94; 0.89-0.99). Neither differences sex or age, moderation effects PRS SES, observed. We preliminary evidence detrimental on behavior, which not modified sex, liability. If confirmed, results reinforce need improving quality, especially around schools, part preventive strategies focused childhood

Language: Английский

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On the importance of parenting in externalizing disorders: an evaluation of indirect genetic effects in families

Journal of Child Psychology and Psychiatry, Journal Year: 2022, Volume and Issue: 63(10), P. 1186 - 1195

Published: July 2, 2022

Background Theoretical models of the development childhood externalizing disorders emphasize role parents. Empirical studies have not been able to identify specific aspects parental behaviors explaining a considerable proportion observed individual differences in problems. The problem is complicated by contribution genetic factors problems, as parents provide both genes and environments their children. We studied joint contributions direct effects children indirect through environment on Methods study used genome‐wide single nucleotide polymorphism data from 9,675 parent–offspring trios participating Norwegian Mother Father child cohort study. Based genomic relatedness matrices, we estimated maternal paternal ADHD, conduct disruptive at 8 years age. Results Models including were preferred for ADHD symptoms inattention hyperactivity, but oppositional defiant behaviors. Direct accounted 11% 24% variance, whereas 0% 16% correlation between effects, or gene–environment correlations, decreased variance with 13% increased 6% hyperactivity Conclusions This provides empirical support notion that significant decrease variation problems correlations would limit number reaching clinical ranges symptoms. Not accounting can lead positive negative bias when identifying variants

Language: Английский

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Building causal knowledge in behavior genetics

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

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