Electronic health records reveal genetics of tobacco use disorder

Official standards for tobacco use cover a variety of behaviors related to tobacco use, such as using more tobacco than intended or continuing to use tobacco despite negative consequences. Genes themselves are known to be associated with nicotine consumption, but these genes don’t tell researchers how nicotine use develops into tobacco use disorder.

“A small percentage of people are able to smoke occasionally without becoming addicted,” Sanchez-Roic said. “We want to understand genetically why occasional smoking becomes the cause of long-term tobacco abuse in some people.”

The researchers leveraged large amounts of electronic health data from multiple U.S. health systems, supported by the PsycheMERGE network, an international consortium of researchers working to synthesize medical records and genomic data to better understand and treat Neuropsychiatric disorders. Sanchez-Roige leads the Substance Use Disorders Working Group within PsycheMERGE.

In the current study, her team used an approach called genome-wide association, which allows researchers to scan the entire genome and look for genetic variants associated with certain traits, behaviors or diseases. This is a method scientists use to find genes associated with smoking, but this is the first time this method has been able to reveal genes associated with tobacco use disorders.

In a study of 898,680 people, they found 461 candidate risk genes for tobacco use disorder, most expressed in the brain. These genes have been linked to many other psychiatric and medical conditions, such as HIV infection, heart disease and chronic pain. Additionally, the researchers were able to verify known findings of genes associated with smoking behavior, which helped validate their approach.

In addition to giving us a more comprehensive understanding of tobacco use disorder, the researchers were also able to use their results to identify hundreds of potential drug candidates that could help doctors treat the disease. However, more research is needed to evaluate these drugs in the laboratory and clinic.

The study also supports a growing belief in genetics research: that electronic health records are an underutilized treasure trove of information.

“There is a wealth of information hidden in medical records, and we are accumulating more information every day as part of routine clinical care,” Sanchez-Roige said. “Because electronic health record data are so difficult to organize and analyze, they are also a relatively untapped resource. This research is part of a growing movement to leverage ever-expanding sources of information to solve complex medical problems.

Study co-authors include: Sylvanus Toikumo, Henry R. Kranzler and Rachel L. Kember of the Department of Veterans Affairs Medical Center Michael J. Crescenz Corporal, Mariela V. Jennings, Benjamin K. Pham, Sevim B Bianchi, John J. Cal. Meredith, Heng Xu, Shreya R. Pakala, Brittany S. Leger and Abraham A. Palmer of the University of San Diego; Hyunjoon Lee, Travis T Mallard and Jordan W Smoller of the Massachusetts General Hospital; Laura Vilar- Ribó, Alexander S. Hatoum and Emma C. Johnson, Washington University School of Medicine, Vanessa Pazdernik, Greg D. Jenkins, Anthony Batzler, Richard Pendegraft, Joanna M. Biernacka, and Brandon J. Coombes, Mayo Clinic, Perel, University of Pennsylvania Zeal Jinwala, Mann School, Maria Niarchou, Vanderbilt University Medical Center, Michael Ehinmowo, University of Ibadan, Penn Medicine Biobank, Million Veterans Project, PsycheMERGE Substance Use Disorders Working Group, Hang Zhou, Yale University School of Medicine Joel Gelernter and Ke Xu, Dana B. Hancock of RTI International, Nancy J. Cox and Lea K. Davis of Vanderbilt University, and Amy C. Justice of Yale University of Public Health.

This research 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 of the completion of this study, Abraham A. Palmer was a member of the Scientific Advisory Board of Vivid Genomics, for which he received stock options.