Executive Function and Impulsivity Predict Distinct Genetic Variance in Internalizing Problems, Externalizing Problems, Thought Disorders, and Compulsive Disorders: A Genomic Structural Equation Modeling Study

Clinical Psychological Science, Journal Year: 2023, Volume and Issue: 12(5), P. 865 - 881

Published: Nov. 9, 2023

Individual differences in self-control predict many health and life outcomes. Building on twin literature, we used genomic structural equation modeling to test the hypothesis that genetic influences executive function impulsivity independent variance mental other The factor (comprising urgency, lack of premeditation, facets) was only modestly genetically correlated with low ( r = .13). Controlling for impulsivity, found associated increased internalizing (β 0.15), externalizing 0.13), thought disorders 0.38), compulsive 0.22), chronotype .011). function, positively 0.36), 0.55), body mass index 0.26), insomnia 0.35) negatively −0.17). Executive were both general cognitive ability educational attainment. This work suggests are separable show associations health.

Language: Английский

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A high-resolution PheWAS approach to alcohol-related polygenic risk scores reveals mechanistic influences of alcohol reinforcing value and drinking motives

Alcohol and Alcoholism, Journal Year: 2024, Volume and Issue: 59(2)

Published: Jan. 17, 2024

Abstract Aims This study uses a high-resolution phenome-wide approach to evaluate the motivational mechanisms of polygenic risk scores (PRSs) that have been robustly associated with coarse alcohol phenotypes in large-scale studies. Methods In community-based sample 1534 Europeans, we examined genome-wide PRSs for Alcohol Use Disorders Identification Test (AUDIT), drinks per week, use disorder (AUD), problematic (PAU), and general addiction, relation 42 curated phenotypes. The were seven categories: consumption, reinforcing value, drinking motives, other addictive behaviors, commonly comorbid psychiatric syndromes, impulsivity, personality traits. Results PRS each phenotype was validated via its within-sample association corresponding (adjusted R2s = 0.35–1.68%, Ps 0.012–3.6 × 10−7) exception AUD. All positively value strongest effects from AUDIT-consumption 0.45–1.33%, 0.006–3.6 10−5) week 0.52–2.28%, 0.004–6.6 10−9). Furthermore, PAU adverse childhood experiences 0.6–0.7%, 0.0001–4.8 10−4). Conclusions These results implicate motives as genetically-influenced using first time. findings also highlight dissecting genetic influence on involvement through diverse phenotypic pathways but need future studies both richness larger samples.

Language: Английский

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Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

Abstract Addiction vulnerability is associated with the tendency to attribute incentive salience reward predictive cues; both addiction and attribution of are influenced by environmental genetic factors. To characterize contributions attribution, we performed a genome-wide association study (GWAS) in cohort 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats Pavlovian conditioned approach task, which characterized individual responses food-associated stimuli (“cues”). Rats exhibited either cue-directed “sign-tracking” behavior or food-cup directed “goal-tracking” behavior. then used reinforcement procedure determine whether would perform novel operant response for unrewarded presentations cue. found that these measures were moderately heritable (SNP heritability, h 2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) 11 12 traits examined. Interval sizes QTLs varied widely. 7 shared QTL on chromosome 1 contained few genes ( e.g. Tenm4 , Mir708 ) have been substance use disorders other mental health humans. Other candidate Wnt11, Pak1 this region had coding variants expression-QTLs mesocorticolimbic regions brain. also conducted Phenome-Wide Association Study (PheWAS) behavioral containing nicotine self-administration separate These results provide starting point molecular dissection further support relationship between drug abuse-related traits.

Language: Английский

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“Weeding out” violence? Translational perspectives on the neuropsychobiological links between cannabis and aggression

Aggression and Violent Behavior, Journal Year: 2024, Volume and Issue: 78, P. 101948 - 101948

Published: April 19, 2024

Language: Английский

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Genome-wide association studies of lifetime and frequency cannabis use in 131,895 individuals

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Cannabis is one of the most widely used drugs globally. Decriminalization cannabis further increasing consumption. We performed genome-wide association studies (GWASs) lifetime (N=131,895) and frequency (N=73,374) use. Lifetime use GWAS identified two loci, near CADM2 (rs11922956, p=2.40E-11) another GRM3 (rs12673181, p=6.90E-09). Frequency locus (rs4856591, p=8.10E-09; r2 =0.76 with rs11922956). Both traits were heritable genetically correlated previous GWASs disorder (CUD), as well other substance cognitive traits. Polygenic scores (PGSs) for associated phenotypes in AllofUs participants. Phenome-wide study PGS a hospital cohort replicated associations mood disorders, uncovered celiac infectious diseases. This work demonstrates value CUD transition risk factors.

Language: Английский

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