title: Linkage analysis followed by association show NRG1 associated with cannabis dependence in African Americans.
abstract: BACKGROUND
  A genetic contribution to cannabis dependence (CaD) has been established but susceptibility genes for CaD remain largely unknown.
  
  
  METHODS
  We employed a multistage design to identify genetic variants underlying CaD. We first performed a genome-wide linkage scan for CaD in 384 African American (AA) and 354 European American families ascertained for genetic studies of cocaine and opioid dependence. We then conducted association analysis under the linkage peak, first using data from a genome-wide association study from the Study of Addiction: Genetics and Environment, followed by replication studies of prioritized single nucleotide polymorphisms (SNPs) in independent samples.
  
  
  RESULTS
  We identified the strongest linkage evidence with CaD (logarithm of odds = 2.9) on chromosome 8p21.1 in AAs. In the association analysis of the Study of Addiction: Genetics and Environment sample under the linkage peak, we identified one SNP (rs17664708) associated with CaD in both AAs (odds ratio [OR] = 2.93, p = .0022) and European Americans (OR = 1.38, p = .02). This SNP, located at NRG1, a susceptibility gene for schizophrenia, was prioritized for further study. We replicated the association of rs17664708 with CaD in an independent AAs sample (OR = 2.81, p = .0068). The joint analysis of the two AA samples demonstrated highly significant association between rs17664708 and CaD with adjustment for either global (p = .00044) or local ancestry (p = .00075).
  
  
  CONCLUSIONS
  Our study shows that NRG1 is probably a susceptibility gene for CaD, based on convergent evidence of linkage and replicated associations in two independent AA samples.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare Center, West Haven, CT 06516, USA.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Han
authors.forename: Bao-Zhu
authors.initials: BZ
authors.lastname: Yang
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: David
authors.initials: D
authors.lastname: Oslin
authors.forename: Raymond
authors.initials: R
authors.lastname: Anton
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D002898:Chromosomes, Human, Pair 8; D030541:Databases, Genetic / Q000706:statistics & numerical data; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000235:genetics*; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020890:Neuregulin-1