ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
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- Integrating SNP data to reveal the adaptive selection features of goat populations in extreme environments.BMC genomics · 2025Article
- Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in a Mouse Knockout Model.Lung · 2024Article
- Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse.Research square · 2024Article
- TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation.The Journal of clinical investigation · 2024Article
- Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease.International journal of molecular sciences · 2023Review
- Assessing the contribution of rare genetic variants to phenotypes of chronic obstructive pulmonary disease using whole-genome sequence data.Human molecular genetics · 2022Article
- Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder.The Lancet. Respiratory medicine · 2022Review
- Genetic evidence for a causative effect of airflow obstruction on left ventricular filling: a Mendelian randomisation study.Respiratory research · 2021Article
- Scavenger Receptor BI Attenuates IL-17A-Dependent Neutrophilic Inflammation in Asthma.American journal of respiratory cell and molecular biology · 2021Article
- Lrp1 Regulation of Pulmonary Function. Follow-Up of Human GWAS in Mice.American journal of respiratory cell and molecular biology · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders.International journal of molecular sciences · 2018Review
- Vagal innervation is required for pulmonary function phenotype inAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitive to serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS.
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