ORCID Profile
0000-0001-6137-5699
Current Organisation
University of California, San Diego
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Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
Publisher: Cold Spring Harbor Laboratory
Date: 08-01-2018
DOI: 10.1101/234294
Abstract: Cannabis use is a heritable trait [1] that has been associated with adverse mental health outcomes. To identify risk variants and improve our knowledge of the genetic etiology of cannabis use, we performed the largest genome-wide association study (GWAS) meta-analysis for lifetime cannabis use (N=184,765) to date. We identified 4 independent loci containing genome-wide significant SNP associations. Gene-based tests revealed 29 genome-wide significant genes located in these 4 loci and 8 additional regions. All SNPs combined explained 10% of the variance in lifetime cannabis use. The most significantly associated gene, CADM2 , has previously been associated with substance use and risk-taking phenotypes [2–4]. We used S-PrediXcan to explore gene expression levels and found 11 unique eGenes. LD-score regression uncovered genetic correlations with smoking, alcohol use and mental health outcomes, including schizophrenia and bipolar disorder. Mendelian randomisation analysis provided evidence for a causal positive influence of schizophrenia risk on lifetime cannabis use.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2201
Publisher: Springer Science and Business Media LLC
Date: 28-09-2022
Publisher: Center for Open Science
Date: 27-10-2022
Abstract: Background: Impulsivity is a multidimensional transdiagnostic construct that is a key feature of many forms of psychopathology, but its underlying latent architecture and genetic correlates remain unclear. Methods: We comprehensively measured impulsivity-related constructs with 105 self-report questionnaire items across 16 scales and subscales in 859 non-clinical adult participants. We used exploratory structural equation modeling and item response theory to measure the target impulsivity traits with high precision. We also calculated polygenic risk scores for impulsivity traits and attention deficit hyperactivity disorder (ADHD) based on genome-wide association studies of independent discovery s les.Results: A hypothesized three-factor model of impulsivity, comprising Disinhibition – affect-free lack of premeditation Urgency – emotion-based rash action and Reward Sensitivity – sensation-, novelty-, and excitement-seeking provided a better fit to the data compared to one- and two-factor models. Disinhibition was associated with impulsivity polygenic risk scores reflecting lack of perseverance (r2 = .017, p = .252 x 10-3) and with ADHD polygenic risk scores (r2 = .014, p =. 826 x 10-3). Reward sensitivity was also associated with ADHD polygenic risk scores (r2 = .018, p = .193 x 10-3). Conclusions: The pattern of observed genetic correlations was consistent with the proposed three-factor model of impulsivity and suggest that disinhibition and reward sensitivity represent independent risk pathways for ADHD, consistent with a dual pathways model. We propose that Disinhibition, Urgency, and Reward Sensitivity represent candidate phenotypes for better understanding the multidimensional nature of Impulsivity.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
Location: United States of America
No related grants have been discovered for Sandra Sanchez-Roige.