Genetics of cortisol secretion and depressive symptoms: A candidate gene and genome wide association approach

Fleur P. Velders, Maris Kuningas, Meena Kumari, Marieke J. Dekker, Andre G. Uitterlinden, Clemens Kirschbaum, Karin Hek, Albert Hofman, Frank C. Verhulst, Mika Kivimaki, Cornelia M. Van Duijn, Brian R. Walker, Henning Tiemeier

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Depressive patients often have altered cortisol secretion, but few studies have investigated genetic variants in relation to both cortisol secretion and depression. To identify genes related to both these conditions, we: (1) tested the association of single nucleotide polymorphisms (SNPs) in hypothalamic pituitary adrenal-axis (HPA-axis) candidate genes with a summary measure of total cortisol secretion during the day (cortisol(AUC)), (2) performed a genome wide association study (GWAS) of cortisol(AUC), and (3) tested the association of identified cortisol-related SNPs with depressive symptoms.

Methods: We analyzed data on candidate SNPs for the HPA-axis, genome-wide scans, cortisol secretion (n = 1711) and depressive symptoms (the Centre for Epidemiology Studies Depression Scale, CES-D) (n = 2928) in elderly persons of the Rotterdam Study. We used data from the Whitehall II study (n = 2836) to replicate the GWAS findings.

Results: Of the 1456 SNPs in 33 candidate genes, minor alleles of 4 SNPs (rs9470080, rs9394309, rs7748266 and rs1360780) in the FKBP5 gene were associated with a decreased cortisol(AUC) (p <1 x 10(-4) after correction for multiple testing using permutations). These SNPs were also associated with an increased risk of depressive symptoms (rs9470080: OR 1.19 (95%Cl 1.0; 1.4)). The GWAS for cortisol yielded 2 SNPs with p-values of 1 x 10(-06) (rs8062512, rs2252459), but these associations could not be replicated.

Conclusions: These results suggest that variation in the FKBP5 gene is associated with both cortisol(AUC) and the likelihood of depressive symptoms. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1053-1061
Number of pages9
JournalPsychoneuroendocrinology
Volume36
Issue number7
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Candidate gene
  • POSTTRAUMATIC-STRESS-DISORDER
  • FKBP5 GENE
  • AGE
  • GWAS
  • FKBP5
  • Salivary cortisol
  • SALIVARY CORTISOL
  • Depressive symptoms
  • COHORT
  • LATE-LIFE
  • PITUITARY-ADRENAL AXIS
  • MAJOR DEPRESSION
  • TREATMENT RESPONSE
  • POLYMORPHISMS

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