A CHRNA5 allele related to nicotine addiction and schizophrenia

L. E. Hong, X. Yang, I. Wonodi, C. A. Hodgkinson, D. Goldman, O. C. Stine, E. S. Stein, G. K. Thaker

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be overrepresented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia, and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) nonsynonymous single nucleotide polymorphism (SNP) rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (P = 0.001) and control smokers (P = 0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (P = 0.022) and African-American (P = 0.006) nonsmoker schizophrenia patients compared with control nonsmokers. Intriguingly, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.

Original languageEnglish (US)
Pages (from-to)530-535
Number of pages6
JournalGenes, Brain and Behavior
Issue number5
StatePublished - Jul 2011
Externally publishedYes


  • α5
  • Comorbidity
  • NAChR
  • Nicotine addiction
  • Schizophrenia
  • Smoking

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology


Dive into the research topics of 'A CHRNA5 allele related to nicotine addiction and schizophrenia'. Together they form a unique fingerprint.

Cite this