The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis

ABSTRACT Background Asthma is a common chronic respiratory disease, and its potential association with the central nervous system has garnered increasing attention in recent years. While observational studies suggest that asthma may affect hippocampal structure and function through mechanisms such a...

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Main Authors: Dandan Han, Shaohua Zhao
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Brain and Behavior
Subjects:
Online Access:https://doi.org/10.1002/brb3.70560
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author Dandan Han
Shaohua Zhao
author_facet Dandan Han
Shaohua Zhao
author_sort Dandan Han
collection DOAJ
description ABSTRACT Background Asthma is a common chronic respiratory disease, and its potential association with the central nervous system has garnered increasing attention in recent years. While observational studies suggest that asthma may affect hippocampal structure and function through mechanisms such as chronic inflammation and hypoxia, its causal relationship remains unclear. Methods In this study, we employed a two‐sample Mendelian randomization (MR) analysis, utilizing large‐scale genome‐wide association study (GWAS) data to systematically investigate the potential causal relationship between asthma and hippocampal volume. Data from a GWAS of asthma involving 155,386 individuals of European ancestry and GWAS imaging‐derived phenotypes (IDPs) of hippocampal volume from 33,219 European individuals were analyzed. Results The results revealed a significant negative correlation between asthma and multiple hippocampal IDPs (PFDR < 0.05), indicating that asthma may contribute to reduced hippocampal volume. We identified 19 independent SNPs significantly associated with asthma (P < 5×10⁻⁸), of which 16 SNPs were retained after clumping (r2 < 0.001) and harmonization. Sensitivity analyses revealed no heterogeneity or horizontal pleiotropy, and reverse MR analysis did not support a causal effect of hippocampal volume on asthma. Conclusion Our study provides genetic evidence for a causal relationship between asthma and changes in hippocampal volume, highlighting the need for closer monitoring and intervention in the neurocognitive health of asthma patients in clinical practice. Future studies should explore the causal relationship between asthma and brain structural changes across different racial groups and asthma subtypes, as well as the underlying biological mechanisms.
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spelling doaj-art-c3b447d8bdd34c299a68041d83380a452025-08-20T03:48:26ZengWileyBrain and Behavior2162-32792025-05-01155n/an/a10.1002/brb3.70560The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization AnalysisDandan Han0Shaohua Zhao1Medical Imaging Center Xuchang Central Hospital Affiliated to Henan University of Science and Technology Xuchang P. R. ChinaDepartment of Plastic Surgery Xuchang Central Hospital Affiliated to Henan University of Science and Technology Xuchang P. R. ChinaABSTRACT Background Asthma is a common chronic respiratory disease, and its potential association with the central nervous system has garnered increasing attention in recent years. While observational studies suggest that asthma may affect hippocampal structure and function through mechanisms such as chronic inflammation and hypoxia, its causal relationship remains unclear. Methods In this study, we employed a two‐sample Mendelian randomization (MR) analysis, utilizing large‐scale genome‐wide association study (GWAS) data to systematically investigate the potential causal relationship between asthma and hippocampal volume. Data from a GWAS of asthma involving 155,386 individuals of European ancestry and GWAS imaging‐derived phenotypes (IDPs) of hippocampal volume from 33,219 European individuals were analyzed. Results The results revealed a significant negative correlation between asthma and multiple hippocampal IDPs (PFDR < 0.05), indicating that asthma may contribute to reduced hippocampal volume. We identified 19 independent SNPs significantly associated with asthma (P < 5×10⁻⁸), of which 16 SNPs were retained after clumping (r2 < 0.001) and harmonization. Sensitivity analyses revealed no heterogeneity or horizontal pleiotropy, and reverse MR analysis did not support a causal effect of hippocampal volume on asthma. Conclusion Our study provides genetic evidence for a causal relationship between asthma and changes in hippocampal volume, highlighting the need for closer monitoring and intervention in the neurocognitive health of asthma patients in clinical practice. Future studies should explore the causal relationship between asthma and brain structural changes across different racial groups and asthma subtypes, as well as the underlying biological mechanisms.https://doi.org/10.1002/brb3.70560asthmabrain imaging‐derived phenotypesgenome‐wide association studyhippocampal volumeMendelian randomization
spellingShingle Dandan Han
Shaohua Zhao
The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
Brain and Behavior
asthma
brain imaging‐derived phenotypes
genome‐wide association study
hippocampal volume
Mendelian randomization
title The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
title_full The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
title_fullStr The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
title_full_unstemmed The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
title_short The Causal Relationship Between Asthma and Hippocampal Volume: A Study Based on Bidirectional Mendelian Randomization Analysis
title_sort causal relationship between asthma and hippocampal volume a study based on bidirectional mendelian randomization analysis
topic asthma
brain imaging‐derived phenotypes
genome‐wide association study
hippocampal volume
Mendelian randomization
url https://doi.org/10.1002/brb3.70560
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