title: Association between promoter methylation of serotonin transporter gene and depressive symptoms: a monozygotic twin study.
abstract: OBJECTIVE
  Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs.
  
  
  METHODS
  DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value).
  
  
  RESULTS
  Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9-7.9, p = .01).
  
  
  CONCLUSIONS
  This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association.
authors.affiliation: School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. jzhao5@tulane.edu
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.forename: Jack
authors.initials: J
authors.lastname: Goldberg
authors.forename: James D
authors.initials: JD
authors.lastname: Bremner
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D003863:Depression / Q000235:genetics* / Q000523:psychology; D003865:Major Depressive Disorder / Q000235:genetics / Q000523:psychology; D044127:Epigenesis, Genetic; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000523:psychology; D014430:Twins, Monozygotic / Q000235:genetics* / Q000523:psychology; D014728:Veterans / Q000523:psychology
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: DNA methylation; SLC6A4; depressive symptoms; monozygotic twins