pubmed.ncbi.nlm.nih.gov

Genetic analysis of impulsive personality traits: Examination of a priori candidates and genome-wide variation - PubMed

Genetic analysis of impulsive personality traits: Examination of a priori candidates and genome-wide variation

Joshua C Gray et al. Psychiatry Res. 2018 Jan.

Abstract

Impulsive personality traits are heritable risk factors and putative endophenotypes for addiction and other psychiatric disorders involving disinhibition. This study examined the genetic basis of impulsive personality traits, defined as scores on the Barratt Impulsiveness Scale (BIS-11) and the UPPS-P Impulsive Behavior Scale (UPPS-P). In 983 healthy young adults of European ancestry, the study examined genetic variation in relation to a combined phenotype of seven subscales based on high phenotypic intercorrelations. The study first tested 14 a priori loci that have previously been associated impulsive personality traits or closely related constructs. Second, the study included an exploratory genome-wide scan (i.e., GWAS), acknowledging that only relatively large effects would be detectable in a sample size of ~ 1000. A priori SNP analyses revealed a significant association between the combined impulsivity phenotype and two SNPs within the 5-HT2a receptor gene (HTR2A; rs6313 and rs6311). Follow-up analyses suggested that the effects were specific to the Motor and Non-planning subscales on the BIS-11, and also that the two loci were in linkage disequilibrium. The GWAS yielded no statistically significant findings. This study further implicates loci within HTR2A with certain forms of self-reported impulsivity and identifies candidates for future investigation from the genome-wide analyses.

Keywords: Endophenotype; Genetics; Impulsivity; Personality traits; Serotonin.

Published by Elsevier B.V.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

The authors do not have any actual or potential conflict of interest to disclose.

Figures

**Figure 1**
Manhattan plot of genome-wide association for impulsive personality traits multivariate regression models with adjustment for sex, age, and site. Significance values were – log₁₀ transformed in order to display the smaller p-values as larger in the figure. The Manhattan plot displays level of significance for each SNP, organized by chromosomal position from chromosomes 1–22. The blue line indicates suggestive significance (10⁻⁵). No SNPs achieve genome-wide significance (p < 5 × 10⁻⁸).

Cited by

Polygenic contributions to performance on the Balloon Analogue Risk Task.
Nurmi EL, Laughlin CP, de Wit H, Palmer AA, MacKillop J, Cannon TD, Bilder RM, Congdon E, Sabb FW, Seaman LC, McElroy JJ, Libowitz MR, Weafer J, Gray J, Dean AC, Hellemann GS, London ED. Nurmi EL, et al. Mol Psychiatry. 2023 Aug;28(8):3524-3530. doi: 10.1038/s41380-023-02123-x. Epub 2023 Aug 15. Mol Psychiatry. 2023. PMID: 37582857 Free PMC article.
CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice.
Sanchez-Roige S, Jennings MV, Thorpe HHA, Mallari JE, van der Werf LC, Bianchi SB, Huang Y, Lee C, Mallard TT, Barnes SA, Wu JY, Barkley-Levenson AM, Boussaty EC, Snethlage CE, Schafer D, Babic Z, Winters BD, Watters KE, Biederer T; 23andMe Research Team; Mackillop J, Stephens DN, Elson SL, Fontanillas P, Khokhar JY, Young JW, Palmer AA. Sanchez-Roige S, et al. Transl Psychiatry. 2023 May 12;13(1):167. doi: 10.1038/s41398-023-02453-y. Transl Psychiatry. 2023. PMID: 37173343 Free PMC article.
Leveraging related health phenotypes for polygenic prediction of impulsive choice, impulsive action, and impulsive personality traits in 1534 European ancestry community adults.
Deng WQ, Belisario K, Gray JC, Levitt EE, Mohammadi-Shemirani P, Singh D, Pare G, MacKillop J. Deng WQ, et al. Genes Brain Behav. 2023 Jun;22(3):e12848. doi: 10.1111/gbb.12848. Epub 2023 Apr 14. Genes Brain Behav. 2023. PMID: 37060189 Free PMC article.
Genomic basis of delayed reward discounting.
Gray JC, Sanchez-Roige S, de Wit H, MacKillop J, Palmer AA. Gray JC, et al. Behav Processes. 2019 May;162:157-161. doi: 10.1016/j.beproc.2019.03.006. Epub 2019 Mar 12. Behav Processes. 2019. PMID: 30876880 Free PMC article. Review.
The Androgen Dehydroepiandrosterone Sulfate Shows a Greater Relationship with Impulsivity than Testosterone in a Healthy Male Sample.
Aluja A, Balada F, García Ó, Aymamí N, García LF. Aluja A, et al. Brain Sci. 2024 Jun 3;14(6):569. doi: 10.3390/brainsci14060569. Brain Sci. 2024. PMID: 38928569 Free PMC article.

References

1. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526:68–74. doi: 10.1038/nature15393. - DOI - PMC - PubMed
1. Agrawal A, Lynskey MT. Are there genetic influences on addiction: evidence from family, adoption and twin studies. Addiction. 2008;103:1069–1081. doi: 10.1111/j.1360-0443.2008.02213.x. - DOI - PubMed
1. Amlung M, Vedelago L, Acker J, Balodis I, MacKillop J. Steep delay discounting and addictive behavior: a meta-analysis of continuous associations. Addiction. 2016;112:51–62. doi: 10.1111/add.13535. - DOI - PMC - PubMed
1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995;57:289–300. doi: 10.2307/2346101. - DOI
1. Benko A, Lazary J, Molnar E, Gonda X, Tothfalusi L, Pap D, Mirnics Z, Kurimay T, Chase D, Juhasz G, Anderson IM, Deakin JFW, Bagdy G. Significant association between the C(-1019)G functional polymorphism of the HTR1A gene and impulsivity. Am J Med Genet Part B, Neuropsychiatr Genet. 2010;153B:592–599. doi: 10.1002/ajmg.b.31025. - DOI - PubMed

Genetic analysis of impulsive personality traits: Examination of a priori candidates and genome-wide variation - PubMed