title: Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence.
abstract: BACKGROUND
  Several lines of evidence in both human and animal studies suggest that variation in neuropeptide Y (NPY) or its receptor genes (NPY1R, NPY2R and NPY5R) is associated with alcohol dependence as well as alcohol withdrawal symptoms. Additional studies suggest that cocaine may affect NPY expression.
  
  
  METHODS
  A total of 39 single nucleotide polymorphisms (SNPs) were genotyped across NPY and its 3 receptor genes in a sample of 1,923 subjects from 219 multiplex alcoholic families of European American descent recruited as part of the Collaborative Studies on the Genetics of Alcoholism (COGA) study. Family-based association analysis was performed to test the primary hypothesis that variation in these genes is associated with alcohol dependence. Secondary analyses evaluated whether there was an association of these SNPs with symptoms of alcohol withdrawal, cocaine dependence, or comorbid alcohol and cocaine dependence.
  
  
  RESULTS
  Although variations in NPY itself were not associated with these phenotypes, variations in 2 NPY-receptor genes were. SNPs in NPY2R provided significant evidence of association with alcohol dependence, alcohol withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence (all p < 0.03). Haplotype analyses strengthened the evidence for these phenotypes (global 0.0004 < p < 0.005). SNPs in NPY5R demonstrated significant association with alcohol withdrawal characterized by seizures (p < 0.05).
  
  
  CONCLUSIONS
  These results indicate that sequence variations in NPY receptor genes are associated with alcohol dependence, particularly a severe subtype of alcohol dependence characterized by withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence.
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.forename: Tiebing
authors.initials: T
authors.lastname: Liang
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
mesh_terms: D000437:Alcoholism / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
chemical_list: D017476:Receptors, Neuropeptide Y