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<1×10(-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%CI 1.0; 1.4)). The GWAS for cortisol yielded 2 SNPs with p-values of 1×10(-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.
journal_name
Psychoneuroendocrinologyjournal_title
Psychoneuroendocrinologyauthors
Velders FP,Kuningas M,Kumari M,Dekker MJ,Uitterlinden AG,Kirschbaum C,Hek K,Hofman A,Verhulst FC,Kivimaki M,Van Duijn CM,Walker BR,Tiemeier Hdoi
10.1016/j.psyneuen.2011.01.003subject
Has Abstractpub_date
2011-08-01 00:00:00pages
1053-61issue
7eissn
0306-4530issn
1873-3360pii
S0306-4530(11)00031-Xjournal_volume
36pub_type
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pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2004-10-01 00:00:00
