Scientists Discover Why Food Allergies Run in Families—And It Could Change Treatment

Researchers at UT Southwestern Medical Center have identified specific genetic mutations that explain why food allergies run in families, offering the first clear genetic roadmap for why some people develop multiple food allergies while others don't. Using advanced DNA sequencing on 56 patients with confirmed allergies to two or more foods, scientists found that nearly 40% carried rare genetic mutations known to increase allergy risk—a discovery that could reshape how doctors diagnose and treat millions of Americans with food allergies.

What Genetic Mutations Are Driving Food Allergies?

The study, published in The Journal of Allergy and Clinical Immunology, used whole exome sequencing—a technique that examines the protein-coding regions of genes—to uncover inherited patterns in food allergy development. The findings revealed that most mutations involved a gene called FLG, which helps maintain the skin's protective barrier. When this barrier weakens, allergens can enter the body more easily and trigger immune responses.

The research also identified something surprising: comprehensive genetic testing found 58% more FLG mutations than traditional genotyping approaches, and it caught variants that older genetic tests often missed, particularly in patients of non-European ancestry. This matters because it means many people with food allergies may have been underdiagnosed or misunderstood by standard testing.

Beyond Skin Barriers: What Else Did Researchers Discover?

While skin barrier genes dominated the findings, researchers uncovered additional genetic clues that hint at a broader story. They identified rare mutations in immune-related genes, including one involved in viral sensing. This discovery supports a long-standing theory in allergy research: early exposure to infections may actually boost the immune system and reduce allergy risk.

"This research shows that advanced DNA testing can uncover clear genetic causes in nearly 4 out of 10 people with multiple food allergies," said Dr. Jeffrey A. SoRelle, Assistant Professor of Pathology and Pediatrics at UT Southwestern, who led the study. The implications are significant because food allergies affect an estimated 33 million Americans and lead to about 3.4 million emergency room visits each year due to anaphylaxis, yet treatment options remain limited.

The genetic discoveries break down into several key categories that researchers identified:

• Skin Barrier Genes: Mutations in FLG and related genes that weaken the skin's protective barrier, allowing allergens to penetrate more easily and trigger immune responses.
• Immune Response Genes: Rare mutations in genes involved in how the immune system senses and responds to viral infections, suggesting a link between infection exposure and allergy development.
• Ancestry-Specific Variants: Genetic mutations that are more common in non-European populations but were previously missed by standard genetic testing methods.

How Could This Change Food Allergy Treatment?

The research team plans to expand their work through UT Southwestern's Sequencing Populations to Accelerate Research and Care (SPARC) program, launched in 2025, to investigate how specific genetic variants influence disease progression and treatment response. The ultimate goal is to move food allergy care toward a more precise, individualized approach that reflects the underlying biology of the condition.

"This study shows that we should be doing more sequencing in the field of food allergy, including for clinical trials and in research centers," Dr. SoRelle explained. The shift toward comprehensive genetic testing could help doctors identify which patients are at highest risk for developing multiple food allergies and tailor prevention or treatment strategies accordingly.

This genetic breakthrough arrives at a pivotal moment in allergy research. Simultaneously, biotech companies are developing new therapies that target the immune cells responsible for allergic reactions. A San Francisco-based company called Excellergy is testing a next-generation anti-IgE therapy designed to disarm mast cells and basophils—the immune cells that trigger allergic reactions—more effectively than existing medications like Xolair. Combined with genetic insights about who is at risk, these emerging treatments could offer patients more targeted and effective options.

For families with a history of food allergies, the message is clear: genetics matter, and advanced testing may soon become a standard part of allergy diagnosis and treatment planning. The research suggests that understanding your family's genetic profile could be the key to preventing or managing food allergies before they develop.