title: The nuclear transcription factor PKNOX2 is a candidate gene for substance dependence in European-origin women.
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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Kelly
authors.initials: K
authors.lastname: Cho
authors.forename: Burton H
authors.initials: BH
authors.lastname: Singer
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D044383:Black People; D016022:Case-Control Studies; D003625:Data Collection / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C435984:PKNOX2 protein, human; D014157:Transcription Factors