Genetic Map of Asthma Unfolds: Chicago Researchers Identify key Differences Between Adult and Childhood Onset
Table of Contents
- 1. Genetic Map of Asthma Unfolds: Chicago Researchers Identify key Differences Between Adult and Childhood Onset
- 2. Decoding the Asthma Genome: A New Approach
- 3. Childhood vs. Adult-Onset: Two Distinct genetic Pathways
- 4. Fine-mapping for Future Treatments
- 5. Implications for personalized Medicine and Drug Development
- 6. How will the integration of genomic data, including chromatin accessibility and eQTLs, contribute too personalized asthma treatment strategies?
- 7. Unlocking Asthma’s Secrets: An Interview with Dr. Anya Sharma
- 8. Interview: Genetic Insights into Asthma Onset
April 10, 2025
A groundbreaking study from the University of Chicago is shedding new light on the genetic underpinnings of asthma, distinguishing meaningful differences between adult-onset and childhood-onset forms of the respiratory disease. The findings, published in Genome Medicine, offer potential new avenues for targeted treatments and personalized medicine.
Decoding the Asthma Genome: A New Approach
Asthma, affecting over 25 million Americans according to the Asthma and Allergy Foundation of America, has long been a puzzle for researchers. Genome-wide association studies (GWAS) have pinpointed numerous genetic regions linked to asthma, but identifying the specific variants with a causal role has remained a challenge. This “variant-to-function” gap has hindered the translation of genetic discoveries into tangible clinical benefits.
Researchers at the University of Chicago tackled this challenge head-on, employing advanced computational tools to analyse GWAS data for both adult-onset and childhood-onset asthma. Their complex approach allowed them to pinpoint genetic variants with a high probability of directly influencing the development of each type of asthma, offering a clearer path toward targeted therapies.
The team’s innovative approach lies in its integration of multiple layers of genomic facts. by incorporating data on chromatin accessibility – the openness of DNA, indicating gene regulatory activity – alongside traditional GWAS findings, the researchers were able to refine their search for causal variants. they further strengthened their analysis by including data on expression quantitative trait loci (eQTLs), which link genetic variants to changes in gene expression. This multi-faceted strategy provided a more thorough picture of the genetic landscape of asthma.
Ethan zhong, a graduate student involved in the study, explained the rationale behind this approach: “The GWAS associations provide sets of variants associated with the disease. So, when those variants overlap with open chromatin regions in cell types that are relevant to asthma pathogenesis like lung epithelial cells, we think that they are more likely to be causal to these asthma phenotypes.”
Childhood vs. Adult-Onset: Two Distinct genetic Pathways
One of the most striking findings of the study is the distinct genetic profiles of adult-onset and childhood-onset asthma. The researchers discovered minimal overlap in the genes implicated in each form of the disease, suggesting that they may arise from fundamentally different biological mechanisms.
According to Carole Ober, PhD, the Blum-Riese Distinguished Service Professor and Chair of human Genetics at UChicago, “The real uniqueness of our study is that the differences between childhood- and adult-onset asthma were evident at every level that we looked at. You find out it’s actually different variants that are contributing to asthma. Even when the GWAS locus looks the same, the genes functionally linked to these variants are also different. So, they’re really quite different diseases.”
This finding could have significant implications for how asthma is diagnosed and treated. Currently, asthma management often follows a one-size-fits-all approach. However, these findings suggest that personalized treatment strategies tailored to the specific genetic profile of each patient may be more effective. For example,a child diagnosed with asthma may benefit from therapies that target the immune system differently than an adult who develops the condition later in life.
| Feature | Childhood-Onset Asthma | Adult-Onset Asthma |
|---|---|---|
| Number of Credible Variant Sets | 67 | 21 |
| Overlap in Variant Sets | Only 16% shared | |
| Candidate Genes Linked to CREs | 169 | 62 |
Fine-mapping for Future Treatments
The researchers used data from the UK Biobank, a comprehensive database containing genetic information from nearly 500,000 individuals in the United Kingdom. This data,combined with a technique called “fine-mapping,” allowed them to pinpoint the most likely causal variants within broader genetic regions associated with asthma.
This process involved integrating data on chromatin accessibility. Open chromatin signifies regions of the genome actively involved in regulating gene expression, which increases the likelihood of a causal link between a genetic variant and asthma.
The fine-mapping analysis revealed 21 self-reliant sets of variants for adult-onset asthma and 67 for childhood-onset asthma,with minimal overlap. Further investigation identified 62 and 169 candidate genes for adult-onset and childhood-onset asthma, respectively, linked to cis-regulatory elements (CREs) – DNA sequences controlling nearby gene expression. Notably, over 60% of these genes exhibited open chromatin in various cell types, including those involved in immune and inflammatory responses.
The team validated their findings by testing six candidate CREs in bronchial epithelial cells.Four of these CREs demonstrated a regulatory effect, confirming the team’s approach was identifying relevant genetic factors.
Implications for personalized Medicine and Drug Development
The study’s findings have significant implications for the future of asthma treatment and prevention. By identifying specific genes and pathways involved in the development of different types of asthma, researchers can now focus on developing targeted therapies that address the underlying causes of the disease.
Such as, if a patient’s genetic profile indicates a high risk for childhood-onset asthma linked to a specific immune pathway, doctors could prescribe preventative treatments that modulate that pathway. Similarly, adults who develop asthma later in life may benefit from therapies that target different inflammatory mechanisms.
The research also opens new avenues for drug development. Pharmaceutical companies can use the identified candidate genes as targets for new medications. By developing drugs that specifically interact with these genes,they can possibly create more effective and safer treatments for asthma.
How will the integration of genomic data, including chromatin accessibility and eQTLs, contribute too personalized asthma treatment strategies?
Unlocking Asthma’s Secrets: An Interview with Dr. Anya Sharma
April 10, 2025
Interview: Genetic Insights into Asthma Onset
Archyde News: Welcome, Dr. Sharma. Thank you for joining us today. Your recent work at the university of Chicago is making important waves. To start, how would you summarize the key findings of your research on the genetic basis of asthma?
Dr.sharma (Lead Researcher): Thank you for having me.Our study has uncovered that childhood-onset and adult-onset asthma are, in many ways, genetically distinct diseases. We found minimal overlap in the genes and pathways involved, suggesting fundamentally different mechanisms driving the disease. This opens doors for personalized treatment strategies.
Archyde News: That’s captivating. Could you elaborate on the methodology you used, notably the integration of genomic data, including chromatin accessibility and eQTLs?
Dr. Sharma: Absolutely.Traditional GWAS studies have identified many genetic regions, but it’s been arduous to pinpoint the exact causal variants. We combined GWAS data with information on chromatin accessibility, which tells us if a gene region is active, and eQTL data. By using this data, we can narrow down the list of genes playing a role and find new treatment paths. This multi-faceted approach provides a clearer picture of how each type of asthma develops.
Archyde News: The study highlights the differences between childhood and adult-onset asthma. What are the immediate implications of these findings for patient care?
Dr. Sharma: The most immediate implication is a shift toward personalized medicine. Currently, asthma treatment is frequently enough a one-size-fits-all approach. Our work suggests that those therapies should be adjusted. It is an approach so that doctors can give treatment that is tailored for the individual based on their genetic makeup. Such as, if the genetic profile of a child indicates high risk for childhood-onset asthma, doctors would then know to focus on those pathways during treatment.
Archyde News: Fine-mapping played a crucial role in pinpointing causal variants. Can you discuss the meaning of this technique in your research?
Dr.Sharma: Fine-mapping, using the UK Biobank data, was essential. It allowed us to narrow down the specific genetic variants within broader regions associated with asthma. We were able to discover genes and cis-regulatory elements, such as those in lung epithelia.This process increased our ability to directly link a genetic variant to asthma risk.
Archyde News: Aside from treatment, what impact would this research have on drug growth?
Dr. sharma: Drug development could take a step toward more specific medications that target the specific identified genes. This would in turn give pharmaceutical companies specific targets to research and work with. This work could lead to the creation of safer and more effective asthma medications for different types of patients.
Archyde News: Thank you for your time and for sharing these incredibly insightful details with us. considering these advancements, what, if any, potential do you think the future hold for asthma prevention and treatment? What will the next 5-10 years bring?
Dr. Sharma: With advancements in genetic analysis, we can create new opportunities for precise treatments. I am confident that we are on the threshold of personalized asthma therapeutics in the next 5-10 years and beyond. A world where treatments are tailored to your genetic makeup and the circumstances surrounding your disease.
