ArticleFrontiers in neuroscience2021
White Matter Integrity and Nicotine Dependence: Evaluating Vertical and Horizontal Pleiotropy.
Article in Frontiers in neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Genetic and neural mechanisms shared by schizophrenia and depression.Molecular psychiatry · 2025Article
- The interaction effects of age, APOE and common environmental risk factors on human brain structure.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Impact of miR-29c-3p in the Nucleus Accumbens on Methamphetamine-Induced Behavioral Sensitization and Neuroplasticity-Related Proteins.International journal of molecular sciences · 2024Article
- An in-depth association analysis of genetic variants within nicotine-related loci: Meeting in middle of GWAS and genetic fine-mapping.Molecular and cellular neurosciences · 2023Article
- Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.Addiction (Abingdon, England) · 2023Article
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Authors and funding
16 authors at 8 institutions in 3 countries.
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Abstract
Tobacco smoking is an addictive behavior that supports nicotine dependence and is an independent risk factor for cancer and other illnesses. Its neurogenetic mechanisms are not fully understood but may act through alterations in the cerebral white matter (WM). We hypothesized that the vertical pleiotropic pathways, where genetic variants influence a trait that in turn influences another trait, link genetic factors, integrity of cerebral WM, and nicotine addiction. We tested this hypothesis using individual genetic factors, WM integrity measured by fractional anisotropy (FA), and nicotine dependence-related smoking phenotypes, including smoking status (SS) and cigarettes per day (CPDs), in a large epidemiological sample collected by the UK Biobank. We performed a genome-wide association study (GWAS) to identify previously reported loci associated with smoking behavior. Smoking was found to be associated with reduced WM integrity in multiple brain regions. We then evaluated two competing vertical pathways: Genes → WM integrity → Smoking versus Genes → Smoking → WM integrity and a horizontal pleiotropy pathway where genetic factors independently affect both smoking and WM integrity. The causal pathway analysis identified 272 pleiotropic single-nucleotide polymorphisms (SNPs) whose effects on SS were mediated by FA, as well as 22 pleiotropic SNPs whose effects on FA were mediated by CPD. These SNPs were mainly located in important susceptibility genes for smoking-induced diseases
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