Genetics, Sex, and Smoking Linked to More Health Issues for IBD Patients

Investigators at Cedars-Sinai have identified risk factors that make inflammatory bowel disease (IBD) patients susceptible to developing serious conditions in other parts of their bodies.

The study is published inthe journal Gastroenterology.

“We found that being female, smoking, or having a history of surgeries to treat Crohn’s disease or ulcerative colitis puts patients more at risk for developing other serious inflammatory conditions,” said Talin Haritunians, PhD, co-senior author of the study and an associate professor of Medicine at Cedars-Sinai.

“Genetic variations of IBD, as well as the location of the disease in the gastrointestinal tract, were also associated with developing debilitating extraintestinal manifestations of the disease affecting the eyes, joints, skin, liver and spine,” Haritunians said.

The multi-center study involved over 12,000 subjects: the largest study of extraintestinal manifestations of IBD to date, according to investigators. The scientists looked at patients who had at least one of seven different conditions occurring outside the gut, including psoriasis, inflammation of the eye, and ankylosing spondylitis, a condition which can degrade the spine or hips.

Investigators also identified genetic, clinical and immunological factors associated with primary sclerosing cholangitis—a condition which damages the liver—and with painful peripheral arthritis that affects both the small and large joints of the body.

“These inflammatory manifestations outside the gut impact about 40% of our patients with IBD. The disorders can have a very significant effect on quality of life and, in some instances, are life-threatening. Our findings will help us identify those at risk of developing these related conditions,” said Dermot McGovern, MD, PhD, the corresponding author of the study and director of Translational Research in the Cedars-Sinai F. Widjaja Inflammatory Bowel Disease Institute. 

McGovern expects the findings will also provide a guide to developing novel therapeutic treatments for the other disorders and may also address the underlying gut inflammation.

“Our clinical findings in this study shed light on the risk factors for morbidity associated with IBD. Our genetic findings highlight pathways that are targets for existing drugs or therapeutics in development. These discoveries are critical for developing more personalized approaches to the management of IBD and its various manifestations,” said McGovern, who holds the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and is the director of Precision Health at Cedars-Sinai.

Other Cedars-Sinai authors involved in the study include Michelle Khrom, Shishir Dube, Gregory J. Botwin, Shaohong Yang, Emebet Mengesha, Dalin Li, Takeo Naito, Nirupama N. Bonthala, Christina Ha, Gil Melmed, Shervin Rabizadeh, Gaurav Syal, Stephan R. Targan Eric Vasiliauskas and David Ziring. Other authors include Millie Long, Lori Robbins, Steven R. Brant, Judy Cho, Richard H. Duerr, John Rioux, Phil Schumm, Mark Silverberg, Ashwin N. Ananthakrishnan, William A. Faubion, Bana Jabri, Sergio A. Lira, Rodney D. Newberry, Robert S. Sandler, Ramnik J. Xavier, Subra Kugathasan, David Hercules and R. Balfour Sartor.

This research was supported in part by by the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. The Cedars-Sinai MIRIAD IBD Biobank is supported by the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) grants (P01 DK046763 and U01 DK062413), and The Leona M and Harry B Helmsley Charitable Trust (DPBM and SHARE Consortium).

Conflict of Interest: Dermot McGovern is a consultant for MERCK, Prometheus Biosciences (acquired by MERCK), Takeda and Prometheus Labs.

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Read more in Discoveries Magazine: Ancestry Matters in IBD