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

Rao, Shuquan; Yao, Yao; Ryan, Joanne; Li, Tao; Wang, Duan; Zheng, Chuan; Xu, Yong; Xu, Qi

doi:10.1038/srep32687

Cited by 54 publications

(37 citation statements)

References 43 publications

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“…The minor allele (T) frequency (MAF) was 23.5% in mothers and 26% in infants. The rs1360780 genotype frequencies were in Hardy-Weinberg equilibrium (χ 2 (2) = 1.23, p = 0.27) and the T allele frequencies here described are comparable to previous studies 13,55,56 . Since the frequency of the homozygote TT genotype was relatively low (7.7% in mothers and 7.1% in infants), we dichotomized samples into "carriers" of the T allele (genotypes CT and TT) and "non-carriers" (CC), as reported in 14.…”

Section: Gene Expression Analyses Gene Expression Analyses Were Condsupporting

confidence: 88%

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach

Ramo-Fernández

Boeck

Koenig

et al. 2019

Sci Rep

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While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CMassociated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation. Childhood maltreatment (CM) is so far an underestimated global phenomenon present in all societies and social classes. CM comprises experiences of physical, sexual and emotional abuse, as well as physical and emotional neglect during childhood and adolescence and constitutes a major threat to the child's mental and physical development with long-term consequences for both mental and somatic health 1-4. The epigenetic alterations in DNA methylation occurring in the aftermath of CM are pivotal for the adaptation to the early life environment 5 , and can thereby affect gene expression levels 6 and molecular responses to environmental stressors. Epigenetic alterations within key player genes of the hypothalamic-pituitary-adrenal (HPA) axis, the main coordinator of the physiological stress response (Fig. 1), are discussed to biologically contribute to health consequences observed in CM-affected individuals 7,8. Accordingly, mounting evidence suggests that CM is associated with alterations in DNA methylation within the glucocorticoid receptor gene (NR3C1) 9-13 and its regulatory co-chaperone FK506-binding protein 51 (FKBP51), which is encoded by the FKBP5 gene 13,14. As depicted in Fig. 1, a balanced regulation between the GR

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Section: Gene Expression Analyses Gene Expression Analyses Were Condsupporting

confidence: 88%

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach

Ramo-Fernández

Boeck

Koenig

et al. 2019

Sci Rep

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“…FKBP5 is considered as a candidate gene for investigating how negative life events may interact with genetic susceptibility to stress-related psychiatric symptoms. This evidence is supported also by a metaanalysis involving 12,491 patients and 14,091 healthy controls which showed as rs4713916 is associated with major depressive disorder susceptibility [63], and thus the major allele (G) is more common among patients than controls. The association was stronger in females than in the whole population.…”

Section: Discussionmentioning

confidence: 61%

FKBP5 Polymorphism, Coping and Emotional Status in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation

Prinzi¹,

Tomino²,

Santoro³

et al. 2019

Preprint

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Background: COPD is characterized by dyspnea, chronic cough, sputum production and extra pulmonary multimorbidity including depression, anxiety and cognitive problems. Methods: Cognitive and psychological clinical alterations/disorders; QoL/Health-related QoL; and Coping strategies were evaluated in 71 COPD patients characterized for FKBP5 gene (rs4713916). Instruments: MMSE, MoCA, ROCF, BDI-II, CES-D, SAS, SF-36, ADL, IADL, SGRQ, MRF 26, CIRS, Brief COPE. Results: Carriers of the rs4713916 polymorphisms (G:A) show better cognitive performances, higher degree of independence in the ADL and IADL, better QoL before and after rehabilitation, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorder, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant anti-psychotic, hypnotic-sedative drugs. On the other hand, no difference was found as regards the number of comorbidities. Conclusions: Our study shows that rs4713916 is positively associated with better outcome for COPD. These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical and behavioral features of COPD patients.. Our data may be used as initial benchmark for future clinical studies.

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“…Meta-analysis was performed in agreement with previously described methods363738. Eligible studies included in the analysis were selected from PubMed, Embase, Medline, ISI Web of Knowledge, ScienceDirect and SCOPUS database by searching the following keywords: zinc finger protein 804A gene or ZNF804A; rs1344706 , SNP or common variants; schizophrenia; bipolar disorder, BD or BPD in varying combinations.…”

Section: Methodsmentioning

confidence: 99%

Genetic association of rs1344706 in ZNF804A with bipolar disorder and schizophrenia susceptibility in Chinese populations

Rao

Yao

Ryan

et al. 2017

Sci Rep

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Rs1344706 in the the zinc finger protein 804A (ZNF804A) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive; furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that rs1344706 showed marginal allelic association with BD (P = 0.028) with T-allele being more prevalent in cases than that in controls (OR = 1.19, 95% CI 1.03–1.37). Meta-analysis of rs1344706 by pooling all available data showed that rs1344706 was significantly associated with BD (P = 0.001). Besides, positive association of rs1344706 with schizophrenia was observed in Northern Chinese (P = 0.005). Furthermore, ZNF804A is highly expressed in human and mouse brains, especially in prenatal stage.

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

Cited by 54 publications

References 43 publications

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach

The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach

FKBP5 Polymorphism, Coping and Emotional Status in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation

Genetic association of rs1344706 in ZNF804A with bipolar disorder and schizophrenia susceptibility in Chinese populations

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