Genetic similarities between tobacco use disorder and related comorbidities: an exploratory study
1 Operational Direction Public Health and Surveillance, Scientific Institute of Public Health, J. Wytsmanstraat 14, 1050, Brussels, Belgium
2 Institute for Public Health Genomics (IPHG), Department of Genetics and Cell Biology, Research Institute GROW (School for Oncology & Developmental Biology), Faculty of Health, Medicine & Life Sciences, Maastricht University, Maastricht, The Netherlands
3 Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands
BMC Medical Genetics 2014, 15:85 doi:10.1186/1471-2350-15-85Published: 24 July 2014
Tobacco use disorder (TUD), defined as the use of tobacco to the detriment of a person’s health or social functioning, is associated with various disorders. We hypothesized that mutual variation in genes may partly explain this link. The aims of this study were to make a non-exhaustive inventory of the disorders using (partially) the same genetic pathways as TUD, and to describe the genetic similarities between TUD and the selected disorders.
We developed a 3 stage approach: (i) selection of genes influencing TUD using Gene2Mesh and Ingenuity Pathway Analysis (IPA), (ii) selection of disorders associated with the selected genes using IPA and (iii) genetic similarities between disorders associated with TUD using Jaccard distance and cluster analyses.
Fourteen disorders and thirty-two genes met our inclusion criteria. The Jaccard distance between pairs of disorders ranged from 0.00 (e.g. oesophageal cancer and malignant hypertension) to 0.45 (e.g. bladder cancer and addiction). A lower number in the Jaccard distance indicates a higher similarity between the two disorders. Two main clusters of genetically similar disorders were observed, one including coexisting disorders (e.g. addiction and alcoholism) and the other one with the side-effects of smoking (e.g. gastric cancer and malignant hypertension).
This exploratory study partly explains the potential genetic components linking TUD to other disorders. Two principle clusters of disorders were observed (i) coexisting disorders of TUD and (ii) side-effects of TUD disorders. A further deepening of this observation in a real life study should allow strengthening this hypothesis.