The nuclear transcription factor PKNOX2 is a candidate gene for substance dependence in European-origin women

PLoS One. 2011 Jan 27;6(1):e16002. doi: 10.1371/journal.pone.0016002.

Abstract

Substance dependence or addiction is a complex environmental and genetic disorder that results in serious health and socio-economic consequences. Multiple substance dependence categories together, rather than any one individual addiction outcome, may explain the genetic variability of such disorder. In our study, we defined a composite substance dependence phenotype derived from six individual diagnoses: addiction to nicotine, alcohol, marijuana, cocaine, opiates or other drugs as a whole. Using data from several genomewide case-control studies, we identified a strong (Odds ratio = 1.77) and significant (p-value = 7E-8) association signal with a novel gene, PBX/knotted 1 homeobox 2 (PKNOX2), on chromosome 11 with the composite phenotype in European-origin women. The association signal is not as significant when individual outcomes for addiction are considered, or in males or African-origin population. Our findings underscore the importance of considering multiple addiction types and the importance of considering population and gender stratification when analyzing data with heterogeneous population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Black People
  • Case-Control Studies
  • Data Collection / methods
  • Female
  • Genetic Predisposition to Disease
  • Genome, Human
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Sex Factors
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / ethnology
  • Substance-Related Disorders / genetics*
  • Transcription Factors / genetics*
  • White People / genetics*

Substances

  • Homeodomain Proteins
  • PKNOX2 protein, human
  • Transcription Factors