title: Case-control association study of WLS variants in opioid and cocaine addicted populations.
abstract: The opioid receptor family is involved in the development and maintenance of drug addiction. The mu-opioid receptor (MOR) mediates the rewarding effects of multiple drugs, including opiates and cocaine. A number of proteins interact with MOR, potentially modulating MOR function and altering the physiological consequences of drug use. These mu-opioid receptor interacting proteins (MORIPs) are potential therapeutic targets for the treatment of addiction. The Wntless (WLS) protein was recently identified as a MORIP in a yeast two-hybrid screen. In this study, we conducted a case-control association analysis of 16 WLS genetic variants in opioid and cocaine addicted individuals of both African-American (opioid n=336, cocaine n=908) and European-American (opioid n=335, cocaine n=336) ancestry. Of the analyzed SNPs, three were nominally associated with opioid addiction and four were nominally associated with cocaine addiction. None of these associations were significant following multiple testing correction. These data suggest that the common variants of WLS analyzed in this study are not associated with opioid or cocaine addiction. However, this study does not exclude the possibilities that rare variants in WLS may affect susceptibility to drug addiction, or that common variants with small effect size may fall below the detection level of our analysis.
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. crist@mail.med.upenn.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Crist
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ambrose-Lanci
authors.forename: Angela
authors.initials: A
authors.lastname: Zeng
authors.forename: Cindy
authors.initials: C
authors.lastname: Yuan
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kampman
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pettinati
authors.forename: David W
authors.initials: DW
authors.lastname: Oslin
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Doyle
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D001741:Black or African American / Q000235:genetics / Q000523:psychology; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009293:Opioid-Related Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D044465:White People / Q000235:genetics / Q000523:psychology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C549111:WLS protein, human