The PCLO gene and depressive disorders: replication in a population-based study.
Previous genome-wide association analysis revealed a new putative candidate gene for major depression: the PCLO gene. Replication in one population-based cohort did not yield genome-wide significance and further replication efforts in clinical studies were unsuccessful. We aimed to validate the association of single-nucleotide polymorphism (SNP) rs2522833 in the PCLO gene with depression in the Rotterdam Study, a prospective population-based cohort of elderly persons. In the Rotterdam Study, we identified 579 persons with a broad depression phenotype (depressive syndromes) of whom 178 cases with DSM-defined depressive disorder. The control group consisted of 912 persons free of depression during the follow-up period and in their histories. Logistic regression analysis showed an association between rs2522833 and depressive disorders (P = 0.0025). However, no association between the broader depressive syndrome group and this SNP was observed (P = 0.20). A meta-analysis combining all studies from the original publication and our study yielded a P-value of 2.16 x 10(-3) for the association between SNP rs2522833 and depressive disorders. However, as in the previous publication, high heterogeneity between studies was observed. Thus, a meta-analysis with the findings from three population-based studies was performed. This demonstrated a genome-wide significant P-value (P = 1.93 x 10(-9)). In conclusion, this study provides additional evidence for an association between PCLO and depressive disorders in a population-based study; no association with a broader syndromal phenotype was observed.
Hek
Karin
K
O3 Research Center, Department of Psychiatry, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.
Mulder
Cornelis L
CL
Luijendijk
Hendrika J
HJ
van Duijn
Cornelia M
CM
Hofman
Albert
A
Uitterlinden
André G
AG
Tiemeier
Henning
H
D003598:Cytoskeletal Proteins / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics*; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
D003598:Cytoskeletal Proteins; D009479:Neuropeptides; C498630:PCLO protein, human