SynthesisJournal of child psychology and psychiatry, and allied disciplines2013
Gene × smoking interactions on human brain gene expression: finding common mechanisms in adolescents and adults.
Synthesis in Journal of child psychology and psychiatry, and allied disciplines, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Structure, function, and pathology of Neurexin-3.Genes & diseases · 2023Review
- Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.Genetic epidemiology · 2020Article
- Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice.Genetics · 2020Article
- A powerful and data-adaptive test for rare-variant-based gene-environment interaction analysis.Statistics in medicine · 2019Article
- Post-mortem molecular profiling of three psychiatric disorders.Genome medicine · 2017Article
- A fast and powerful W-test for pairwise epistasis testing.Nucleic acids research · 2016Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundNumerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets to assess if DNA variation is associated with post-mortem brain gene expression changes based on smoking behavior, a biobehavioral construct that is part of a complex system of genetic and environmental influences.
methodsWe conducted an expression quantitative trait locus (eQTL) study on two independent human brain gene expression datasets assessing G × E for selected psychiatric genes and smoking status. We employed linear regression to model the significance of the Gene × Smoking interaction term, followed by meta-analysis across datasets.
resultsOverall, we observed that the effect of DNA variation on gene expression is moderated by smoking status. Expression of 16 genes was significantly associated with single nucleotide polymorphisms that demonstrated G × E effects. The strongest finding (p = 1.9 × 10⁻¹¹) was neurexin 3-alpha (NRXN3), a synaptic cell-cell adhesion molecule involved in maintenance of neural connections (such as the maintenance of smoking behavior). Other significant G × E associations include four glutamate genes.
conclusionsThis is one of the first studies to demonstrate G × E effects within the human brain. In particular, this study implicated NRXN3 in the maintenance of smoking. The effect of smoking on NRXN3 expression and downstream behavior is different based upon SNP genotype, indicating that DNA profiles based on SNPs could be useful in understanding the effects of smoking behaviors. These results suggest that better measurement of psychiatric conditions, and the environment in post-mortem brain studies may yield an important avenue for understanding the biological mechanisms of G × E interactions in psychiatry.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.