Association of Neurexin 3 polymorphisms with smoking behavior

E. Docampo, M. Ribasés, M. Gratacòs, E. Bruguera, C. Cabezas, C. Sánchez-Mora, G. Nieva, D. Puente, J. M. Argimon-Pallàs, M. Casas, R. Rabionet, Xavier P. Estivill

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The Neurexin 3 gene (NRXN3) has been associated with dependence on various addictive substances, as well as with the degree of smoking in schizophrenic patients and impulsivity among tobacco abusers. To further evaluate the role of NRXN3 in nicotine addiction, we analyzed single nucleotide polymorphisms (SNPs) and a copy number variant (CNV) within the NRXN3 genomic region. An initial study was carried out on 157 smokers and 595 controls, all of Spanish Caucasian origin. Nicotine dependence was assessed using the Fagerström index and the number of cigarettes smoked per day. The 45 NRXN3 SNPs genotyped included all the SNPs previously associated with disease, and a previously described deletion within NRXN3. This analysis was replicated in 276 additional independent smokers and 568 controls. Case-control association analyses were performed at the allele, genotype and haplotype levels. Allelic and genotypic association tests showed that three NRXN3 SNPs were associated with a lower risk of being a smoker. The haplotype analysis showed that one block of 16 Kb, consisting of two of the significant SNPs (rs221473 and rs221497), was also associated with lower risk of being a smoker in both the discovery and the replication cohorts, reaching a higher level of significance when the whole sample was considered [odds ratio = 0.57 (0.42-0.77), permuted P = 0.0075]. By contrast, the NRXN3 CNV was not associated with smoking behavior. Taken together, our results confirm a role for NRXN3 in susceptibility to smoking behavior, and strongly implicate this gene in genetic vulnerability to addictive behaviors.

Original languageEnglish
Pages (from-to)704-711
Number of pages8
JournalGenes, Brain and Behavior
Volume11
Issue number6
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

Fingerprint

Smoking
Single Nucleotide Polymorphism
Genes
Haplotypes
Addictive Behavior
Tobacco Use Disorder
Gene Dosage
Impulsive Behavior
Nicotine
Tobacco Products
Tobacco
Alleles
Odds Ratio
Genotype

Keywords

  • Addiction
  • Association
  • NRXN3
  • Smoking
  • SNP

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Docampo, E., Ribasés, M., Gratacòs, M., Bruguera, E., Cabezas, C., Sánchez-Mora, C., ... Estivill, X. P. (2012). Association of Neurexin 3 polymorphisms with smoking behavior. Genes, Brain and Behavior, 11(6), 704-711. https://doi.org/10.1111/j.1601-183X.2012.00815.x

Association of Neurexin 3 polymorphisms with smoking behavior. / Docampo, E.; Ribasés, M.; Gratacòs, M.; Bruguera, E.; Cabezas, C.; Sánchez-Mora, C.; Nieva, G.; Puente, D.; Argimon-Pallàs, J. M.; Casas, M.; Rabionet, R.; Estivill, Xavier P.

In: Genes, Brain and Behavior, Vol. 11, No. 6, 08.2012, p. 704-711.

Research output: Contribution to journalArticle

Docampo, E, Ribasés, M, Gratacòs, M, Bruguera, E, Cabezas, C, Sánchez-Mora, C, Nieva, G, Puente, D, Argimon-Pallàs, JM, Casas, M, Rabionet, R & Estivill, XP 2012, 'Association of Neurexin 3 polymorphisms with smoking behavior', Genes, Brain and Behavior, vol. 11, no. 6, pp. 704-711. https://doi.org/10.1111/j.1601-183X.2012.00815.x
Docampo E, Ribasés M, Gratacòs M, Bruguera E, Cabezas C, Sánchez-Mora C et al. Association of Neurexin 3 polymorphisms with smoking behavior. Genes, Brain and Behavior. 2012 Aug;11(6):704-711. https://doi.org/10.1111/j.1601-183X.2012.00815.x
Docampo, E. ; Ribasés, M. ; Gratacòs, M. ; Bruguera, E. ; Cabezas, C. ; Sánchez-Mora, C. ; Nieva, G. ; Puente, D. ; Argimon-Pallàs, J. M. ; Casas, M. ; Rabionet, R. ; Estivill, Xavier P. / Association of Neurexin 3 polymorphisms with smoking behavior. In: Genes, Brain and Behavior. 2012 ; Vol. 11, No. 6. pp. 704-711.
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