UCSF, Kaiser Permanente Study Identifies Genetic Susceptibility for Hernia

By Kristen Bole

An incarcerated inguinal hernia on a cross sectional CT scan

An incarcerated inguinal hernia as seen on cross sectional CT scan. Image by James Heilman, MD via Wikimedia Commons

In the first large-scale genetic study of hernia risk in adults, researchers at University of California, San Francisco (UCSF) and Kaiser Permanente have identified variations at four locations in the genome that underlie the risk of inguinal hernia, the most common type of hernia.

“Surgical repair of inguinal hernias is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop them,” said co-lead author Eric Jorgenson, PhD, research scientist at the Kaiser Permanente Division of Research. “These findings provide insight into the origins of hernia development and highlight genetic pathways for studies of its treatment.”

The study appears in the Dec. 21 issue of Nature Communications.

Abdominal hernias are one of the most frequently diagnosed conditions in clinical practice, of which inguinal hernias are the most prevalent. More than 750,000 surgeries are conducted in the U.S. annually to treat the condition, for which risk increases with age. Overall, men have a 27 percent lifetime risk of developing an inguinal hernia, while women have 6 percent lifetime risk.

Researchers conducted a genome-wide association study (GWAS) among participants in Kaiser Permanente’s Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort who had surgically-confirmed inguinal hernias. The GERA project, which was conducted in collaboration with UCSF, is one of the nation’s largest and most diverse genomics projects, linking genetic data to electronic medical records for more than 110,000 members who have voluntarily participated, enabling investigations into many diseases and conditions.

The top associations in the four regions were replicated in a large independent sample of research participants with self-reported hernia repair surgery from 23andMe, a personal genomics and biotechnology company based in Mountain View, California. The 23andMe cohort provided informed consent under an approved protocol. Researchers at UCSF then analyzed the expression of genes in these regions in mice.

Nadav Ahituv, PhD

Nadav Ahituv, PhD

Nadja Makki, PhD

Nadja Makki, PhD

“We observed expression of four genes in these regions in mouse connective tissue, which suggests they could have a role in hernia development,” explained Nadav Ahituv, PhD, associate professor in the Department of Bioengineering and Therapeutic Sciences, in the UCSF schools of Pharmacy and Medicine. “We also found through network analyses that at least two of these genes operate in the same biological pathway, pointing to new areas of investigation.”

A hernia is usually a sac formed by the lining of the abdominal cavity. The sac comes through a hole or weak area in the layer of the abdominal wall that surrounds the muscle, known as the fascia. Depending on their severity, hernias can strangulate blood vessels or a section of the bowel, cutting off blood flow and posing a risk of obstruction. Emergency hernia surgery to treat these conditions is associated with a substantial risk of death. A subset of patients experience hernia recurrence and chronic pain after surgery.

“Taken together, our findings suggest that these four new regions affect the development of inguinal hernias through the regulation of both collagen and elastin maintenance,” added co-lead author Nadja Makki, PhD, a member of the Ahituv lab.

“Further research into the precise mechanisms through which these regions act may improve our understanding of hernia formation and point the way to more effective preventative, operative and non-surgical treatments of this common disorder,” Jorgenson concluded.

Additional authors of the study include Ling Shen and Andrew Avins, MD, MPH, Kaiser Permanente Division of Research; Walter L. Eckalbar, PhD, Department of Bioengineering and Therapeutic Sciences, UCSF; David C. Chen, MD, David Geffen School of Medicine at UCLA; and David Hinds, 23andMe Inc.

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, the Division’s 550+ staff are working on more than 350 ongoing research studies in behavioral health and aging, cancer, cardiovascular and metabolic conditions, health care delivery and policy, infectious diseases, vaccine safety and effectiveness, and women's and children's health.

About UCSF

UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and UCSF Health, which includes two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco, as well as other partner and affiliated hospitals and healthcare providers throughout the Bay Area. Please visit www.ucsf.edu/news.