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No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis.

ABSTRACT: Major depressive disorder (MDD) is a complex psychiatric condition with strong genetic predisposition. The association of MDD with genetic polymorphisms, such as Val66Met (rs6265), in the brain derived neurotrophic factor (BDNF), have been reported in many studies and the results were conflicting. In this study, we performed a systematic literature search and conducted random-effects meta-analysis to evaluate genetic variants in BDNF with MDD. A gene-based analysis was also conducted to investigate the cumulative effects of genetic polymorphisms in BDNF. A total of 28 studies from 26 published articles were included in our analysis. Meta-analysis yielded an estimated odds ratio (OR) of 0.96 (95% CI: 0.89-1.05; P = 0.402) for Val66Met (rs6265), 0.83 (95% CI: 0.67-1.04; P = 0.103) for 11757C/G, 1.16 (95% CI: 0.74-1.82; P = 0.527) for 270T/C, 1.03 (95% CI: 0.18-5.75; P = 0.974) for 712A/G and 0.98 (95% CI: 0.85-1.14; P = 0.831) for rs988748. The gene-based analysis indicated that BDNF is not associated with MDD (P > 0.21). Our updated meta- and novel gene-based analyses provide no evidence of the association of BDNF with major depression.

SUBMITTER: Gyekis JP

PROVIDER: S-EPMC3725128 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis.

Gyekis Joseph P JP Yu Weihong W Dong Shuqian S Wang Haina H Qian Jun J Kota Pravina P Yang Jingyun J

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20121126 1

Major depressive disorder (MDD) is a complex psychiatric condition with strong genetic predisposition. The association of MDD with genetic polymorphisms, such as Val66Met (rs6265), in the brain derived neurotrophic factor (BDNF), have been reported in many studies and the results were conflicting. In this study, we performed a systematic literature search and conducted random-effects meta-analysis to evaluate genetic variants in BDNF with MDD. A gene-based analysis was also conducted to investig ...[more]

PMID: 23184535

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Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Project description:BACKGROUND:The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results. METHODS:A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants in LTF were available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by using random-effects models to assess the association of genetic variants in LTF with the risk of dental caries. We also performed a gene-based analysis to explore the joint association of multiple genetic variants in LTF with the risk of dental caries. RESULTS:Our systematic literature search identified six relevant papers for analysis. We found no significant association between rs1126478 and the risk of dental caries when meta-analysing the genotype distribution between subjects with dental caries and those without dental caries (additive model: OR?=?1.41; 95% CI?=?0.98-2.02; P?=?0.065). However, further analysis indicated that rs1126478 was associated with dental risk in subjects who had moderate or severe dental caries compared to those without dental caries (P?<?0.0001). The gene-based analysis indicated that multiple genetic variants in LTF were jointly associated with the risk of dental caries (P?=?0.002). CONCLUSIONS:The present meta-analysis revealed some evidence of the association between rs1126478 and dental caries and that multiple genetic variants in LTF are jointly associated with the risk of dental caries. Our findings need to be validated by larger studies that adjust for important confounding factors for the risk of dental caries.

Dataset Information

No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis.

Publications

No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis.

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