Identification of pleiotropic genes and biological mechanisms underlying the shared genetic component between asthma, neuropsychiatric disorders, and substance use behaviors
- 1Paris City University, INSERM, HealthFex, Genomic Epidemiology of Multifactorial Diseases Group
Abstract
Asthma patients suffer from neuropsychiatric disorders (NPDs) more often than expected and NPD patients have a higher prevalence of smoking, which can lead to asthma. To investigate the genetic mechanisms underlying this complex relationship, we performed an integrative analysis of GWAS summary statistics from four asthma subtypes, 12 NPDs, and six substance use behaviors (SUBs). Asthma shares an important genetic component with post-traumatic stress disorder (PTSD), major depressive disorder, and attention-deficit/hyperactivity disorder (ADHD) that cannot be fully accounted for by smoking. Multi-trait GWAS identified 354 independent variants mapping to 178 pleiotropic genes capturing the core of the shared genetics of asthma, NPD, and SUB. Single-cell transcriptomic analysis across blood, brain, and lung tissues revealed pleiotropic gene overexpression in 57 cell types and three candidate mechanisms linking asthma and NPDs. First, immune-related pleiotropic genes are expressed in microglia, blood and lung immune cells, suggesting shared immune dysfunction. Second, the pleiotropic genes EP300, RERE, and MAML3 regulate NOTCH signaling and are expressed in neurons, microglia, and lymphoid progenitors. Third, pleiotropic genes expressed in ciliated cells of both lung and brain implicate ciliary dysfunction. These findings may help identify new treatment strategies for patients with co-occurring asthma and neuropsychiatric disorders.
Related
- Identification of a pleiotropic QTL and candidate genes underlying ear traits of maize (Zea mays L.) through controlling the activity of inflorescence meristem
- Reconciling intrinsic and ecosystem water-use efficiency reveals physiological mechanisms underlying carbon-water coupling across biological scales
- Design, synthesis and biological evaluation of pleiotropic prodrugs activated by cholinesterases and releasing a 5-HT4R agonist, with in vivo antiamnesic activity
- Mathematical model for visual cortical development based on molecular mechanisms underlying the generation and elimination of dendritic spines
- Dietary Modulation of Neurobiological Mechanisms Underlying Executive Function and Decision-Making: A Systematic Review
BibTeX
@misc{huang2026identification,
title = {{Identification of pleiotropic genes and biological mechanisms underlying the shared genetic component between asthma, neuropsychiatric disorders, and substance use behaviors}},
author = {H. Huang and R. Vernet and L. Troubat and C. Linhard and L. Chataigner and Y. Suzuki and S. Fischer and h. Aschard and F. Demenais and E. Bouzigon and H. Julienne},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.26364574},
url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26364574v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Identification of pleiotropic genes and biological mechanisms underlying the shared genetic component between asthma, neuropsychiatric disorders, and substance use behaviors
AU - H. Huang
AU - R. Vernet
AU - L. Troubat
AU - C. Linhard
AU - L. Chataigner
AU - Y. Suzuki
AU - S. Fischer
AU - h. Aschard
AU - F. Demenais
AU - E. Bouzigon
AU - H. Julienne
PY - 2026
DA - 2026/10/16
PB - medRxiv
DO - 10.64898/2026.10.16.26364574
UR - https://www.medrxiv.org/content/10.64898/2026.10.16.26364574v1
AB - Asthma patients suffer from neuropsychiatric disorders (NPDs) more often than expected and NPD patients have a higher prevalence of smoking, which can lead to asthma. To investigate the genetic mechanisms underlying this complex relationship, we performed an integrative analysis of GWAS summary statistics from four asthma subtypes, 12 NPDs, and six substance use behaviors (SUBs). Asthma shares an important genetic component with post-traumatic stress disorder (PTSD), major depressive disorder, and attention-deficit/hyperactivity disorder (ADHD) that cannot be fully accounted for by smoking. Multi-trait GWAS identified 354 independent variants mapping to 178 pleiotropic genes capturing the core of the shared genetics of asthma, NPD, and SUB. Single-cell transcriptomic analysis across blood, brain, and lung tissues revealed pleiotropic gene overexpression in 57 cell types and three candidate mechanisms linking asthma and NPDs. First, immune-related pleiotropic genes are expressed in microglia, blood and lung immune cells, suggesting shared immune dysfunction. Second, the pleiotropic genes EP300, RERE, and MAML3 regulate NOTCH signaling and are expressed in neurons, microglia, and lymphoid progenitors. Third, pleiotropic genes expressed in ciliated cells of both lung and brain implicate ciliary dysfunction. These findings may help identify new treatment strategies for patients with co-occurring asthma and neuropsychiatric disorders.
ER -