title: CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.
abstract: BACKGROUND
  Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol.
  
  
  METHODS
  32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland.
  
  
  RESULTS
  The CLOCK haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between CLOCK and AUD.
  
  
  CONCLUSIONS
  Our findings suggest an association between the CLOCK gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the CLOCK variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Neurogenetics Unit CMM L8:00 Karolinska University Hospital, 171 76 Stockholm, Sweden. louise.sjoholm@ki.se.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Sjöholm
authors.forename: Leena
authors.initials: L
authors.lastname: Kovanen
authors.forename: Sirkku T
authors.initials: ST
authors.lastname: Saarikoski
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen