title: ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.
abstract: BACKGROUND
  Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology.
  
  
  METHODS
  A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans.
  
  
  RESULTS
  Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51 × 10(-8)). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption.
  
  
  CONCLUSIONS
  The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, Hunan Normal University, Changsha, Hunan 410081, China.
authors.forename: Xiang-ding
authors.initials: XD
authors.lastname: Chen
authors.forename: Dong-hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Tie-lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yu-fang
authors.initials: YF
authors.lastname: Pei
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Tan
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Xiao-gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Shu-feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Ning
authors.forename: Xue-zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D001798:Blood Proteins; D016207:Cytokines; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*
chemical_list: C102999:ANKRD7 protein, human; D001798:Blood Proteins; C412483:CYTL1 protein, human; D016207:Cytokines; D009687:Nuclear Proteins; D011506:Proteins; D018121:Receptors, Cytokine; C113554:cytokine-like factor-1