Official standards for tobacco use include a variety of behaviors associated with tobacco use, such as using more cigarettes than intended and continuing to use despite negative effects . Although genes associated with nicotine intake itself are known, these do not tell researchers how nicotine use progresses to tobacco use disorder.
“Some people can smoke occasionally without developing an addiction,” Sánchez-Roige says. “We want to understand from a genetic perspective why occasional tobacco use becomes chronic misuse for some people.”
The researchers leveraged large amounts of electronic health data from several U.S. health systems. This was made possible by his PsycheMERGE Network, an international consortium of researchers aimed at integrating medical records and genomics data for a better understanding and treatment of neuropsychiatric diseases. Sanchez-Roige leads the Substance Use Disorders Workgroup within PsycheMERGE.
For the current study, her team used an approach called genome-wide association. This allows researchers to scan the entire genome looking for mutations in genes associated with specific traits, behaviors, or diseases. This is one of several approaches scientists have used to find genes associated with smoking, but this is the first time this approach has been able to uncover genes associated with smoking disorders.
A study of 898,680 people found 461 candidate risk genes for tobacco use disorder, most of which are expressed in the brain. These genes have been linked to a myriad of other psychiatric conditions and medical conditions, including HIV infection, heart disease, and chronic pain. Additionally, the researchers were able to test known findings about genes associated with smoking behavior, which helped validate their approach.
In addition to providing a more comprehensive view of tobacco use disorder, researchers will use their results to identify hundreds of drug candidates that could help doctors treat the disease. I was able to. However, further research is needed to evaluate these agents in the laboratory and clinical setting.
But the study also supports a growing idea in the field of genetics research that electronic medical records are a treasure trove of underutilized information.
“There is a tremendous amount of information hidden in medical records, and we accumulate more information every day as part of routine clinical care,” said Sánchez-Roige. “Electronic health record data is also a relatively untapped resource because it is very difficult to organize and analyze. This research aims to harness this ever-expanding source of information to solve complex medical problems. It’s part of a growing movement.”
Co-authors of the study include Sylvanus Toikumo, Henry R. Kranzler, Rachel L. Kember of the Michael J. Crescenz Veterans Affairs Medical Center Corporal, Mariela V. Jennings, and Benjamin K. Pham. , Mr. Sevim B. Bianchi, and Mr. John J. Kember. Meredith, Heng Xu, Shreya R. Pacara, Brittany S. Ledger, and Abraham A. Palmer of the University of California, San Diego; Hyunjun Lee, Travis T. Mallard, and Jordan W. Smoller of Massachusetts General Hospital; Laura Villar Ribo of the Autonomous University of Barcelona; S. Hatoum and Emma C. Johnson of the Alexander Washington University School of Medicine; Vanessa Pazdelnik, Greg D. Jenkins, Anthony Butzler, Richard Pendegraft, and Joanna M. of the Mayo Clinic; Biernacka, Brandon J. Coombs, Zille Zinwala, MD, University of Pennsylvania Perelman School, Maria Niarchow, Vandebilt University Medical Center, Michael Ehinmowo, University of Ibadan, Penn Medicine Biobank, Million Veterans Program , PsycheMERGE Substance Use Disorders Workgroup, Han Zhou, Joel Gelernter, Ke Xu, Dana B. of Yale School of Medicine; Hancock of RTI International; Nancy J. Cox and Lee K. Davis of Vanderbilt University, Yale; Amy C. Justice of the College of Public Health;
This study was funded in part by the California Tobacco-Related Disease Research Program (grants T29KT0526 and T32IR5226) and the National Institute on Drug Abuse (grant DP1DA054394).
Disclosure: At the time this research was completed, Abraham A. Palmer was a member of the scientific advisory board of Vivid Genomics and received stock options.
