The PCLO gene and depressive disorders: replication in a population-based study
The PCLO gene and depressive disorders: replication in a population-based study
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DOI：
10.1093/hmg/ddp529
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发表时间：
2010-02-15
影响因子：
3.5
通讯作者：
Tiemeier, Henning
中科院分区：
文献类型：
--
作者：
Hek, Karin;Mulder, Cornelis L.;Tiemeier, Henning
先前的全基因组关联分析揭示了一个新的可能的抑郁症候选基因：PCLO基因。在一个基于人群的队列中进行复制并没有产生全基因组意义，临床研究中的进一步复制努力也没有成功。我们的目标是在鹿特丹研究中验证PCLO基因的单核苷酸多态(SNP)rs2522833与抑郁症的相关性，鹿特丹研究是一项基于人群的前瞻性老年人队列研究。在鹿特丹的研究中，我们确定了579名具有广泛抑郁表型(抑郁综合征)的人，其中178人患有DSM定义的抑郁障碍。对照组包括912名在随访期和他们的病史中没有抑郁的人。Logistic回归分析显示rs2522833与抑郁障碍相关(P=0.0025)。然而，没有观察到更广泛的抑郁综合征组与这种SNP之间的关联(P=0.20)。Meta分析结合了最初发表的所有研究和我们的研究，得出了SNP rs2522833与抑郁障碍之间的P值为2.16 x 10(-3)。然而，正如先前发表的那样，研究之间的高度异质性被观察到。因此，对三项以人群为基础的研究结果进行了荟萃分析。这显示了全基因组的显著P值(P=1.93×10(-9))。总之，在一项基于人群的研究中，这项研究为PCLO和抑郁障碍之间的关联提供了额外的证据；没有观察到与更广泛的综合征表型之间的关联。
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.