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

Delay discounting—the extent to which individuals show a preference for smaller immediate rewards over larger delayed rewards—has been proposed as a transdiagnostic neurocognitive process across mental health conditions, but its examination in relation to posttraumatic stress disorder (PTSD) is comparatively recent. To assess the aggregated evidence for elevated delay discounting in relation to posttraumatic stress, we conducted a meta-analysis on existing empirical literature. Bibliographic searches identified 209 candidate articles, of which 13 articles with 14 independent effect sizes were eligible for meta-analysis, reflecting a combined sample size of N = 6897. Individual study designs included case-control (e.g. examination of differences in delay discounting between individuals with and without PTSD) and continuous association studies (e.g. relationship between posttraumatic stress symptom severity and delay discounting). In a combined analysis of all studies, the overall relationship was a small but statistically significant positive association between posttraumatic stress and delay discounting (r =.135, p <.0001). The same relationship was statistically significant for continuous association studies (r =.092, p =.027) and case-control designs (r =.179, p <.001). Evidence of publication bias was minimal. The included studies were limited in that many did not concurrently incorporate other psychiatric conditions in the analyses, leaving the specificity of the relationship to posttraumatic stress less clear. Nonetheless, these findings are broadly consistent with previous meta-analyses of delayed reward discounting in relation to other mental health conditions and provide further evidence for the transdiagnostic utility of this construct. [ABSTRACT FROM AUTHOR]

Impulsivity refers to a number of conceptually related phenotypes reflecting self‐regulatory capacity that are considered promising endophenotypes for mental and physical health. Measures of impulsivity can be broadly grouped into three domains, namely, impulsive choice, impulsive action, and impulsive personality traits. In a community‐based sample of ancestral Europeans (n = 1534), we conducted genome‐wide association studies (GWASs) of impulsive choice (delay discounting), impulsive action (behavioral inhibition), and impulsive personality traits (UPPS‐P), and evaluated 11 polygenic risk scores (PRSs) of phenotypes previously linked to self‐regulation. Although there were no individual genome‐wide significant hits, the neuroticism PRS was positively associated with negative urgency (adjusted R2 = 1.61%, p = 3.6 × 10−7) and the educational attainment PRS was inversely associated with delay discounting (adjusted R2 = 1.68%, p = 2.2 × 10−7). There was also evidence implicating PRSs of attention‐deficit/hyperactivity disorder, externalizing, risk‐taking, smoking cessation, smoking initiation, and body mass index with one or more impulsivity phenotypes (adjusted R2s: 0.35%–1.07%; FDR adjusted ps = 0.05–0.0006). These significant associations between PRSs and impulsivity phenotypes are consistent with established genetic correlations. The combined PRS explained 0.91%–2.46% of the phenotypic variance for individual impulsivity measures, corresponding to 8.7%–32.5% of their reported single‐nucleotide polymorphism (SNP)‐based heritability, suggesting a non‐negligible portion of the SNP‐based heritability can be recovered by PRSs. These results support the predictive validity and utility of PRSs, even derived from related phenotypes, to inform the genetics of impulsivity phenotypes. [ABSTRACT FROM AUTHOR]