Genetic and environmental pathways to complex diseases

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...

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Bibliographic Details
Published in:BMC systems biology 2009-05, Vol.3 (46), p.46-46, Article 46
Main Authors: Gohlke, Julia M, Thomas, Reuben, Zhang, Yonqing, Rosenstein, Michael C, Davis, Allan P, Murphy, Cynthia, Becker, Kevin G, Mattingly, Carolyn J, Portier, Christopher J
Format: Article
Language:English
Subjects:
Databases, Genetic
Disease - genetics
Diseases
Environment
Environmental aspects
Evolution, Molecular
Gene expression
Gene Expression Regulation
Genetic aspects
Genome-Wide Association Study
Genotype
Health aspects
Humans
Mental Disorders - etiology
Mental Disorders - genetics
Mental Disorders - metabolism
Mental Disorders - pathology
Metabolic Diseases - etiology
Metabolic Diseases - genetics
Metabolic Diseases - metabolism
Metabolic Diseases - pathology
Phenotype
Public health
Transcription, Genetic
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Summary: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.
ISSN:1752-0509
1752-0509
DOI:10.1186/1752-0509-3-46