Genetic and environmental pathways to complex diseases.
Genetic and environmental pathways to complex diseases.
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DOI：
10.1186/1752-0509-3-46
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发表时间：
2009-05-05
影响因子：
--
通讯作者：
Portier CJ
中科院分区：
文献类型：
--
作者：
Gohlke JM;Thomas R;Zhang Y;Rosenstein MC;Davis AP;Murphy C;Becker KG;Mattingly CJ;Portier CJ
复杂疾病的发病机制涉及遗传和环境因素随时间的整合，使得使用传统的实验方法来梳理表型、基因型和环境因素之间的关系变得特别困难。利用以基因为中心的数据库，我们通过识别与遗传和环境贡献相关的关键分子途径，开发了一个复杂疾病和环境因素的网络。与已知的化学疾病的关系和转录调控的分析，从基因表达数据集的几个环境因素和表型聚集在代谢综合征和神经精神子网的比较支持我们的网络假设。该分析确定了天然和合成的类维生素A、抗精神病药物、Omega 3脂肪酸和拟除虫菊酯农药作为通过PPAR和脂肪细胞因子信号传导的代谢综合征表型的潜在环境调节剂，以及有机磷农药作为神经精神表型的潜在环境调节剂。确定整合遗传和环境调节剂的关键调控途径，确定与疾病相关的目标，这将允许有效筛选大量环境因素，筛选可以为进一步研究确定优先事项，并指导公共卫生决策。
Pathogenesis of complex diseases involves the integration of genetic and environmental factors over time, making it particularly difficult to tease apart relationships between phenotype, genotype, and environmental factors using traditional experimental approaches. Using gene-centered databases, we have developed a network of complex diseases and environmental factors through the identification of key molecular pathways associated with both genetic and environmental contributions. Comparison with known chemical disease relationships and analysis of transcriptional regulation from gene expression datasets for several environmental factors and phenotypes clustered in a metabolic syndrome and neuropsychiatric subnetwork supports our network hypotheses. This analysis identifies natural and synthetic retinoids, antipsychotic medications, Omega 3 fatty acids, and pyrethroid pesticides as potential environmental modulators of metabolic syndrome phenotypes through PPAR and adipocytokine signaling and organophosphate pesticides as potential environmental modulators of neuropsychiatric phenotypes. Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions.
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影响因子：
3.5
作者：
Bordoni, Alessandra;Astolfi, Annalisa;Pession, Annalisa
通讯作者：
Pession, Annalisa
影响因子：
46.9
作者：
Butte, AJ;Kohane, IS
通讯作者：
Kohane, IS
影响因子：
64.8
作者：
Hovatta, I;Tennant, RS;Barlow, C
通讯作者：
Barlow, C
小鼠端脑发育过程中原神经基因调控网络的表征。
影响因子：
5.4
作者：
Gohlke JM;Armant O;Parham FM;Smith MV;Zimmer C;Castro DS;Nguyen L;Parker JS;Gradwohl G;Portier CJ;Guillemot F
通讯作者：
Guillemot F
影响因子：
30.8
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
通讯作者：
Bertram, Lars