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      Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis

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          Abstract

          Previous studies have investigated the association between common variants in FKBP5 and MDD; however, the results remain inconsistent. In order to conduct a comprehensive meta-analysis of the association between FKBP5 variants and MDD risk, seven studies involving 26582 subjects, including 12491 cases with MDD and 14091 controls, were enrolled totally. Four common SNPs (rs1360780, rs4713916, rs3800373 and rs755658) with complete data from two or more studies were analyzed. In the total sample, there was no evidence of a significant association between MDD and any of the four SNPs using a random-effects model. However, after removing one heterogeneous German study, as indicated by sensitivity analysis, both the rs1360780 T-allele (Z = 2.95, P = 0.003, OR = 1.06, 95% CI = 1.02–1.11) and the rs3800373 C-allele (Z = 3.05, P = 0.002, OR = 1.07, 95% CI 1.02–1.12) were significantly associated with MDD in a fixed-effect model. Our study thus provides support for an association between specific FKBP5 genetic variants and MDD risk. Rs4713916 was not significantly associated with MDD; However, this analysis had limited statistical power and larger sample sizes are required to further validate this result. Future research should also investigate possible gender- and ethnicity-specific differences in the association between FKBP5 and MDD.

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          Most cited references29

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          Evidence-based health policy--lessons from the Global Burden of Disease Study.

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            Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project.

            To describe the 12-month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries. A representative random sample of non-institutionalized inhabitants from Belgium, France, Germany, Italy, the Netherlands and Spain aged 18 or older (n = 21425) were interviewed between January 2001 and August 2003. DSM-IV disorders were assessed by lay interviewers using a revised version of the Composite International Diagnostic Interview (WMH-CIDI). Fourteen per cent reported a lifetime history of any mood disorder, 13.6% any anxiety disorder and 5.2% a lifetime history of any alcohol disorder. More than 6% reported any anxiety disorder, 4.2% any mood disorder, and 1.0% any alcohol disorder in the last year. Major depression and specific phobia were the most common single mental disorders. Women were twice as likely to suffer 12-month mood and anxiety disorders as men, while men were more likely to suffer alcohol abuse disorders. ESEMeD is the first study to highlight the magnitude of mental disorders in the six European countries studied. Mental disorders were frequent, more common in female, unemployed, disabled persons, or persons who were never married or previously married. Younger persons were also more likely to have mental disorders, indicating an early age of onset for mood, anxiety and alcohol disorders.
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              Genetic epidemiology of major depression: review and meta-analysis.

              The authors conducted a meta-analysis of relevant data from primary studies of the genetic epidemiology of major depression. The authors searched MEDLINE and the reference lists of previous review articles to identify relevant primary studies. On the basis of a review of family, adoption, and twin studies that met specific inclusion criteria, the authors derived quantitative summary statistics. Five family studies met the inclusion criteria. The odds ratios for proband (subjects with major depression or comparison subjects) versus first-degree relative status (affected or unaffected with major depression) were homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 95% CI=2.31-3.49). No adoption study met the inclusion criteria, but the results of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteria, and their statistical summation suggested that familial aggregation was due to additive genetic effects (point estimate of heritability of liability=37%, 95% CI=31%-42%), with a minimal contribution of environmental effects common to siblings (point estimate=0%, 95% CI=0%-5%), and substantial individual-specific environmental effects/measurement error (point estimate=63%, 95% CI=58%-67%). The literature suggests that recurrence best predicts the familial aggregation of major depression. Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depression is a complex disorder that does not result from either genetic or environmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally applicable.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                07 September 2016
                2016
                : 6
                : 32687
                Affiliations
                [1 ]School of Life Science and Engineering, Southwest Jiaotong University , Chengdu 610031, China
                [2 ]Department of Fundamental Medicine, Chengdu University of Traditional Chinese Medicine , Chengdu 611137, China
                [3 ]Disease Epigenetics Group, Murdoch Childrens Research Institute & Department of Paediatrics, University of Melbourne , 3052 Parkville, Victoria, Australia
                [4 ]Inserm, U1061, Univ Montpellier , F-34093 Montpellier, France
                [5 ]Mental Health Center, West China Hospital/West China School of Medicine, Sichuan University , Chengdu, 610041, China
                [6 ]Department of Orthopedics, West China Hospital/West China School of Medicine, Sichuan University , Chengdu, 610041, China
                [7 ]Department of Psychiatry, First Clinical Medical College/First Hospital of Shanxi Medical University , Taiyuan, 030000, China
                [8 ]National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 10005, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep32687
                10.1038/srep32687
                5013409
                27601205
                0a820249-49bc-442e-a0aa-a12fc724912c
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 24 February 2016
                : 12 August 2016
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