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

SummaryBackgroundDepressive 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 (cortisolAUC), (2) performed a genome wide association study (GWAS) of cortisolAUC, and (3) tested the association of identified cortisol-related SNPs with depressive symptoms.MethodsWe 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.ResultsOf 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 cortisolAUC (p