The PCLO gene and depressive disorders: replication in a population-based study.

Area of Science:

• Genetics
• Psychiatry
• Epidemiology

Background:

• Previous genome-wide association studies (GWAS) identified the PCLO gene as a potential candidate for major depression.
• Replication attempts in one cohort and clinical studies failed to confirm genome-wide significance for PCLO.
• The PCLO gene's role in major depression requires further validation in diverse populations.

Purpose of the Study:

• To validate the association of single-nucleotide polymorphism (SNP) rs2522833 in the PCLO gene with depression.
• To investigate the association in a prospective, population-based cohort of elderly individuals (the Rotterdam Study).
• To perform meta-analyses to consolidate findings and assess genome-wide significance.

Main Methods:

• The Rotterdam Study cohort included 579 individuals with depressive syndromes (178 with DSM-defined depressive disorder) and 912 controls.
• Logistic regression analysis was used to assess the association between SNP rs2522833 and depressive disorders.
• Meta-analyses were conducted, first combining initial publication data with the Rotterdam Study, then including three population-based studies.

Main Results:

• A significant association was found between rs2522833 and DSM-defined depressive disorders (P = 0.0025) in the Rotterdam Study.
• No association was observed between rs2522833 and the broader depressive syndrome phenotype (P = 0.20).
• A meta-analysis of three population-based studies yielded genome-wide significant results (P = 1.93 x 10(-9)), despite high heterogeneity.

Conclusions:

• This study provides additional evidence supporting the association between the PCLO gene and depressive disorders in a population-based sample.
• The association appears specific to diagnosed depressive disorders, not broader depressive syndromes.
• Combined population-based study meta-analysis achieved genome-wide significance, reinforcing PCLO as a key gene in major depression.