title: Association study of DKK2 polymorphisms with alcohol dependence and alcohol-related harm.
abstract: BACKGROUND
  Alcohol dependence (AD) is a common disorder with both environmental and genetic factors. Previous studies have shown that the genomic region from chromosome 4q22-q32 is closely associated with AD. Furthermore, a study with Irish subjects revealed that the polymorphisms of Dickkopf WNT signaling pathway inhibitor (DKK2), located at 4q25, showed a significant association with AD.
  
  
  METHODS
  We conducted a replication study of the association between DKK2 polymorphisms and AD with 459 alcoholics and 444 normal controls, all of Korean descendent. To rank the AD of the subjects, Alcohol Use Disorders Identification Test (AUDIT) was utilized. Using the TaqMan assay, 21 single-nucleotide polymorphisms (SNPs) of DKK2 were genotyped.
  
  
  RESULTS
  Our analysis showed that rs17037102 (Q146R) was significantly associated with overall AUDIT score (p = 0.003, p(corr)  = 0.05 in dominant model). Further analysis showed that the SNP was significantly associated with alcohol-related harm (p = 0.001, p(corr)  = 0.02 in co-dominant model). Several other SNPs, including the 3 SNPs which were associated with AD in European population, showed marginal associations that were erased when corrections for multiple testing was applied. Furthermore, rs17037102 was in linkage disequilibrium with the nonexonic DKK2 SNPs which showed associations with AD in the previous study with Irish population, which suggests that rs17037102 may be the causal SNP.
  
  
  CONCLUSIONS
  We found 1 DKK2 SNP to be significantly associated with alcohol-related harm in alcoholic subjects. The SNP might be the causal SNP which led its linked SNPs to show associations in previous studies.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jason Yongha
authors.initials: JY
authors.lastname: Kim
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Jee Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Boung Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Ihn-Geun
authors.initials: IG
authors.lastname: Choi
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000465:Algorithms; D026661:Clinical Trials Data Monitoring Committees; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012044:Regression Analysis; D056910:Republic of Korea; D055815:Young Adult
chemical_list: C498622:DKK2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D004247:DNA
keywords: Alcohol Use Disorders Identification Test; Alcohol-Related Harm; DKK2; Polymorphism