Genetic Study of Impulsiveness Reveals Link with Psychiatric Disorders

Summary: Researchers have identified a genetic link between impulsivity and a predisposition to engage in risky behaviors.

Source: SfN.

Impulsiveness and substance use share a genetic basis, according to genome-wide association studies published in Journal of Neuroscience by academic and industry researchers. With more than 20,000 participants, the research represents the largest genetic analysis of impulsive personality traits to date.

Dr. Abraham Palmer and colleagues compared genetic data with self-reported impulsive personality traits and history of drug experimentation from a large sample of older adults of European ancestry participating in personal genetics company 23andMe’s research program.

The researchers identified an association between variants in the gene CADM2 — previously implicated in risky preference, alcohol consumption, and cannabis use — and sensation seeking and drug experimentation history. They also identified an association between a gene previously implicated in schizophrenia risk (CACNA1I) and negative urgency — a tendency to act impulsively in the face of adversity.

These findings demonstrate how an individual’s genetic makeup may predispose them to engage in risky behavior, including drug use and, potentially, misuse. Additional studies of younger and more diverse populations could provide additional insights into the genetics and consequences of impulsive personality traits.

Manhattan plot of GWAS results indicating the strongest associations between the 22 autosomes, X chromosome, and UPPSP negative urgency.
NeuroscienceNews.com image is credited to Sanchez-Roige et al., JNeurosci (2019).

About this neuroscience research article

Funding: The research was funded by the Peter Boris Chair in Addictions Research, NIH/National Institute on Drug Abuse, University of California San Diego, California Tobacco-Related Disease Research Program.

Source: David Barnstone – SfN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is Sanchez-Roige et al., JNeurosci (2019).
Original Research: Abstract for “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” by Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, Joshua C. Gray, Harriet de Wit, James MacKillop and Abraham A. Palmer in Journal of Neuroscience. Published February 4 2019.
doi:10.1523/JNEUROSCI.2662-18.2019

Cite This NeuroscienceNews.com Article
SfN”Genetic Study of Impulsiveness Reveals Link with Psychiatric Disorders.” NeuroscienceNews. NeuroscienceNews, 44 February 2019.
<http://neurosciencenews.com/impulsiveness-genetics-psychiatry-10681/>.
SfN(2019, February 44). Genetic Study of Impulsiveness Reveals Link with Psychiatric Disorders. NeuroscienceNews. Retrieved February 44, 2019 from http://neurosciencenews.com/impulsiveness-genetics-psychiatry-10681/
SfN”Genetic Study of Impulsiveness Reveals Link with Psychiatric Disorders.” http://neurosciencenews.com/impulsiveness-genetics-psychiatry-10681/ (accessed February 44, 2019).

Abstract

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

Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse and attention-deficit/hyperactivity disorder (ADHD). In collaboration with the genetics company 23andMe, Inc., we performed 10 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 had tried in their lifetime) in up to 22,861 male and female adult human research participants of European ancestry. Impulsive personality traits and Drug Experimentation showed SNP-heritabilities that ranged from 5-11%. Genetic variants in the CADM2 locus were significantly associated with UPPSP Sensation Seeking (p=8.3×10-9, rs139528938) and showed a suggestive association with Drug Experimentation (p=3.0×10-7, rs2163971; r2=0.68 with rs139528938). Furthermore, genetic variants in the CACNA1I locus were significantly associated with UPPSP Negative Urgency (p=3.8×10-8, rs199694726). The role of these genes was supported by single variant, gene- and transcriptome-based analyses. 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 ADHD (rg=0.30-0.51), supporting their validity as endophenotypes. 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.

SIGNIFICANCE STATEMENT

Impulsive personality traits (IPT) are heritable traits that are governed by frontal-subcortical circuits and are associated with neuropsychiatric disorders, particularly substance use disorders. We have performed GWAS of IPT to identify regions and genes that account for this heritable variation. IPT and Drug Experimentation were modestly heritable (5-11%). We identified an association between SNPs in CADM2 and both Sensation Seeking and Drug Experimentation; and between variants in CACNA1I and Negative Urgency. The role of these genes was supported by single variant, gene- and transcriptome-based analyses. This study provides evidence that impulsivity can be genetically separated into distinct components. We showed that IPT are genetically associated with substance use and ADHD, suggesting impulsivity is an endophenotype contributing to these psychiatric conditions.

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