Role of Environmental Confounding in the Association between FKBP5 and First-Episode Psychosis.
Role of Environmental Confounding in the Association between FKBP5 and First-Episode Psychosis.
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DOI：
10.3389/fpsyt.2014.00084
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发表时间：
2014
影响因子：
4.7
通讯作者：
Iyegbe C
中科院分区：
文献类型：
--
作者：
Ajnakina O;Borges S;Di Forti M;Patel Y;Xu X;Green P;Stilo SA;Kolliakou A;Sood P;Marques TR;David AS;Prata D;Dazzan P;Powell J;Pariante C;Mondelli V;Morgan C;Murray RM;Fisher HL;Iyegbe C
背景资料：未能解释通常发生在精神科队列中的病因多样性可能会增加混淆的可能性，因为遗传方差的比例将特定于在病例中具有不同分布的暴露。这项研究调查了是否最大限度地减少这种混淆的可能性，加强了目前在全基因组水平上不支持的遗传候选人的证据。研究方法：291例来自英国南伦敦的首发精神病病例和218例未受影响的对照进行了FKBP 5基因rs 1360780位点功能多态性的评价。使用逻辑回归对FKBP 5与精神病之间的关系进行建模。大麻使用（大麻经历问卷）和父母分离（儿童期护理和虐待经历问卷）作为混杂因素纳入分析。结果如下：在rs 1360780处的关联未被检测到，直到在模型中调整了两个环境因素的影响（OR = 2.81，95%CI 1.23-6.43，p = 0.02）。rs 1360780和父母分离之间的统计学相互作用通过分层检验证实（OR = 2.8，p = 0.02 vs. OR = 0.89，p = 0.80）。遗传主效应与其他（压力相关）临床表型的结果方向一致。此外，效应幅度的变化可以通过与模型中使用的不同大麻结构相关的功率水平来解释（r = 0.95）。结论：我们的研究结果表明，FKBP 5基因变异影响精神病易感性的程度可能取决于其他病因因素。这一发现需要在大型独立队列中进一步验证。这项工作可能具有转化意义;根据对先前环境暴露的逐案理解来区分遗传病因的能力将赋予重要的临床优势，这将有利于提供个性化的治疗策略。
Background: Failure to account for the etiological diversity that typically occurs in psychiatric cohorts may increase the potential for confounding as a proportion of genetic variance will be specific to exposures that have varying distributions in cases. This study investigated whether minimizing the potential for such confounding strengthened the evidence for a genetic candidate currently unsupported at the genome-wide level. Methods: Two hundred and ninety-one first-episode psychosis cases from South London, UK and 218 unaffected controls were evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. The relationship between FKBP5 and psychosis was modeled using logistic regression. Cannabis use (Cannabis Experiences Questionnaire) and parental separation (Childhood Experience of Care and Abuse Questionnaire) were included as confounders in the analysis. Results: Association at rs1360780 was not detected until the effects of the two environmental factors had been adjusted for in the model (OR = 2.81, 95% CI 1.23–6.43, p = 0.02). A statistical interaction between rs1360780 and parental separation was confirmed by stratified tests (OR = 2.8, p = 0.02 vs. OR = 0.89, p = 0.80). The genetic main effect was directionally consistent with findings in other (stress-related) clinical phenotypes. Moreover, the variation in effect magnitude was explained by the level of power associated with different cannabis constructs used in the model (r = 0.95). Conclusion: Our results suggest that the extent to which genetic variants in FKBP5 can influence susceptibility to psychosis may depend on other etiological factors. This finding requires further validation in large independent cohorts. Potentially this work could have translational implications; the ability to discriminate between genetic etiologies based on a case-by-case understanding of previous environmental exposures would confer an important clinical advantage that would benefit the delivery of personalizable treatment strategies.
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影响因子：
6.9
作者：
Konings, M.;Stefanis, N.;Henquet, C.
通讯作者：
Henquet, C.
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