title: Association of a polyadenylation polymorphism in the serotonin transporter and panic disorder.
abstract: BACKGROUND
  Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD.
  
  
  METHODS
  Quantitative polymerase chain reaction on human brain samples (n = 65) and lymphoblast cultures (n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases (n = 307) and a control sample (n = 542) that has similar population structure.
  
  
  RESULTS
  The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain (p < .001) and lymphoblasts (p < .001). The balance of the polyadenylation forms is also associated with gender in brain only (p < .05). Association testing of rs3813034 in PD identified a significant association (p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively.
  
  
  CONCLUSIONS
  rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.
authors.affiliation: Department of Psychiatry, Weill Medical College of Cornell University, New York, New York, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gyawali
authors.forename: Ryan
authors.initials: R
authors.lastname: Subaran
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
authors.forename: Dylan
authors.initials: D
authors.lastname: Hershkowitz
authors.forename: Morgan C
authors.initials: MC
authors.lastname: McKenna
authors.forename: Ardesheer
authors.initials: A
authors.lastname: Talati
authors.forename: Abby J
authors.initials: AJ
authors.lastname: Fyer
authors.forename: Priya
authors.initials: P
authors.lastname: Wickramaratne
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Adams
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hodge
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Schmidt
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bannon
authors.forename: Charles E
authors.initials: CE
authors.lastname: Glatt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D016584:Panic Disorder / Q000235:genetics* / Q000473:pathology; D026723:Polyadenylation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013223:Statistics as Topic
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins