Understanding Heritability in Childhood Autoimmune Diseases

Heritability plays more of a factor in pediatric-onset autoimmune diseases than in adult diseases.

A recent study has revealed more precise statistics about the heritability of 9 autoimmune diseases that begin in childhood, which could lead to better predictions of a child’s risk for these conditions.

Autoimmune diseases affect approximately 1 in 12 people in the Western world and are a significant cause of chronic disability.

“The results from this study enable us to better understand the genetic component of these diseases and how they are genetically related to each other, thereby explaining why different autoimmune disorders often run in the same family,” said study lead Hakon Hakonarson, MD, PhD, professor of Pediatrics and director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia (CHOP).

The research focused on 9 pediatric-onset autoimmune diseases (pAIDS), including type 1 diabetes, celiac disease, juvenile idiopathic arthritis, common variable immunodeficiency, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, and ankylosing spondylitis.

Researchers compared genome-wide association study data for these conditions with data from non-autoimmune diseases. Overall, the researchers analyzed data from over 5000 pAID patients extracted from the CHOP pediatric network, along with data from 36,000 healthy individuals.

Historically, clinicians have suspected the existence of an overlapping genetic landscape due to the fact that many autoimmune diseases are genetic and individual patients often suffer from more than 1 condition.

The current study used up-to-date research tools for the quantitative analysis, calculating the percentages that specific gene variants contribute to each disease. Additionally, the researchers measured joint heritability attributable to common gene variants shared by pairs of diseases.

Type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA) were the 2 diseases with the highest heritability, according to the study. Ulcerative colitis and Crohn’s disease had lower rates of heritability.

This finding was previously observed in prior research that showed the influence of environmental factors, such as gastrointestinal microorganisms, in those diseases.

Stronger heritability was detected among pAIDs than in adult-onset autoimmune diseases, which may be attributable to the fact that children have had less time than adults for environmental factors to play a significant role in development, the study noted.

Among disease pairs, ulcerative colitis and Crohn’s disease had the strongest correlations, as did JIA and common variable immunodeficiency.

Findings from a previous study led by Hakonarson earlier this year indicated opportunities for drug targeting and for advancing the potential of precision medicine to individualize therapies based on a patient’s genetic profile.

“We envision that we may be able to develop new therapies that may help significant subsets of patients across multiple autoimmune diseases who share the same genetic variants that result in perturbations of normal biological functions and autoimmunity,” Hakonarson said. “This is the foundation for precision medicine approaches.”