Genome-wide association studies of impulsive personality traits (BIS-11 and UPPSP) and drug experimentation in up to 22,861 adult research participants identify loci in the CACNA1I and CADM2 genes
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Abstract
Abstract Background Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse. Methods In collaboration with the genetics company 23andMe, Inc., we performed several genome-wide association studies ( GWAS ) on measures of impulsive personality traits (the short version of the UPPSP Impulsive Behavior Scale, and the Barratt Impulsiveness Scale [BIS-11]) and drug experimentation (the number of drug classes an individual has tried in their lifetime) in up to 22,861 male and female adult research participants of European ancestry. Results Impulsive personality traits and drug experimentation showed SNP-heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with the UPPSP Sensation Seeking subscale ( P = 8.3 × 10 -9 , rs139528938) and showed a suggestive association with drug experimentation ( P = 3.0 × 10 -7 , rs2163971; r 2 = 0.68 with rs139528938); CADM2 has been previously associated with measures of risky behaviors and self-reported risk tolerance, cannabis initiation, alcohol consumption, as well as information speed processing, body mass index (BMI) variation and obesity. Furthermore, genetic variants in the CACNA1I locus were significantly associated with the UPPSP Negative Urgency subscale ( P = 3.8 × 10 -8 , rs199694726). Multiple subscales from both UPPSP and BIS showed strong genetic correlations (>0.5) with drug experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPSP and BIS subscales were genetically correlated with attention-deficit/hyperactivity disorder (r g = 0.30-0.51, p < 8.69 x 10 -3 ), supporting their validity as endophenotypes. Conclusions Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.
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Other genes among the 34, including CADM2, ZIC4, GABRA2, NEGR1, and FURIN, have previously been identified in GWAS of behavioral or psychiatric traits.
“Other genes among the 34 have previously been identified in GWAS of behavioral or psychiatric traits: Cell Adhesion Molecule 2 (CADM2, previously identified in GWAS related to self-regulation, including drug use and risk tolerance17,33), Zic Family Member 4 (ZIC4, associated with brain volume34), Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha 2 (GABRA2; the site of action for alcohol and”
From Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction. (2021) · cites this paper as [33]
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References 89 · Cited by 143
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- Authors
- Sanchez-Roige, S., Fontanillas, P., Elson, S. L., Gray, J. C., de Wit, H., MacKillop, J., & Palmer, A. A.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Homewood Research Institute (CA)
- University of California San Diego (US)
- Corresponding author
- Palmer, Abraham A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-02-04
- Volume
- 39
- Issue
- 13
- Pages
- 2662-18
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6435820
- OpenAlex
- W2914248456
- Cited by
- 143
- References
- 89
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 19 · 2023: 19 · 2022: 20 · 2021: 16 · 2020: 43 · 2019: 12 · 2018: 2
- FWCI
- 13.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R25MH081482)
- National Institute on Drug Abuse (R01DA002812, P50DA037844)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- trait impulsivity, drug experimentation, CADM2, sensation seeking, negative urgency, Barratt Impulsiveness Scale, UPPS-P, attention deficit hyperactivity disorder, genetic correlation, substance use, smoking initiation, cannabis use, endophenotypes, heritability, single nucleotide polymorphisms, frontal-subcortical circuits
- MeSH terms
- Glucagon-Like Peptide-2 Receptor, Female, Humans, Impulsive Behavior, Male, Middle Aged, Peptides, Personality, Personality Tests, Cell Adhesion Molecules, Polymorphism, Single Nucleotide, Calcium Channels, T-Type, White People, Drug Users, Genome-Wide Association Study
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