Cytokine-induced molecular responses in airway smooth muscle cells inform genome-wide association studies of asthma.

Genome Medicine
Emma E ThompsonRamaswamy Krishnan

Abstract

A challenge in the post-GWAS era is to assign function to disease-associated variants. However, available resources do not include all tissues or environmental exposures that are relevant to all diseases. For example, exaggerated bronchoconstriction of airway smooth muscle cells (ASMCs) defines airway hyperresponsiveness (AHR), a cardinal feature of asthma. However, the contribution of ASMC to genetic and genomic studies has largely been overlooked. Our study aimed to address the gap in data availability from a critical tissue in genomic studies of asthma. We developed a cell model of AHR to discover variants associated with transcriptional, epigenetic, and cellular responses to two AHR promoting cytokines, IL-13 and IL-17A, and performed a GWAS of bronchial responsiveness (BRI) in humans. Our study revealed significant response differences between ASMCs from asthma cases and controls, including genes implicated in asthma susceptibility. We defined molecular quantitative trait loci (QTLs) for expression (eQTLs) and methylation (meQTLs), and cellular QTLs for contractility (coQTLs) and performed a GWAS of BRI in human subjects. Variants in asthma GWAS were significantly enriched for ASM QTLs and BRI-associated SNPs, and near gen...Continue Reading

References

Sep 3, 1998·Molecular Biology of the Cell·V Vouret-CraviariE Van Obberghen-Schilling
Apr 20, 2002·Current Opinion in Allergy and Clinical Immunology·Yassine Amrani, Reynold A Panettieri
Nov 5, 2003·British Journal of Pharmacology·Omar TlibaYassine Amrani
May 14, 2004·Current Opinion in Pharmacology·Stephanie A Shore
Oct 23, 2004·Science·UNKNOWN ENCODE Project Consortium
Sep 6, 2007·Genome Research·Sorin DraghiciRoberto Romero
Aug 9, 2008·American Journal of Respiratory Cell and Molecular Biology·Yoshihiko ChibaMiwa Misawa
Nov 8, 2008·Bioinformatics·Adi Laurentiu TarcaRoberto Romero
Jun 2, 2009·American Journal of Respiratory and Critical Care Medicine·Prescott G WoodruffJohn V Fahy
Feb 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fred D FinkelmanMarsha Wills-Karp
May 19, 2010·Cardiovascular Research·Qiang ShenSarah Y Yuan
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Apr 5, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul-André RisseJames G Martin
Aug 16, 2011·The Journal of Allergy and Clinical Immunology·Caroline A MotikaCarole Ober
Apr 12, 2012·Bioinformatics·Andrey A Shabalin
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Jul 11, 2012·Pulmonary Pharmacology & Therapeutics·Behzad YeganehBrian G G Oliver
Jan 12, 2013·Journal of Applied Physiology·Diana C Doeing, Julian Solway
Aug 13, 2013·Genome Research·Michele DonatoSorin Draghici
Aug 30, 2013·BMC Medical Genetics·Blanca E HimesScott T Weiss
Jan 8, 2014·American Journal of Respiratory Cell and Molecular Biology·Stéphane DragonAbdelilah S Gounni
Sep 2, 2014·The Journal of Allergy and Clinical Immunology·Nirav R Bhakta, David J Erle
Jan 7, 2015·American Journal of Respiratory and Critical Care Medicine·Elliot IsraelUNKNOWN SHARP Investigators
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Feb 20, 2015·Nature·UNKNOWN Roadmap Epigenomics ConsortiumManolis Kellis
Mar 4, 2015·PLoS Computational Biology·Oren E LivneDan L Nicolae
May 20, 2015·Nature Genetics·Tinca J C PoldermanDanielle Posthuma
Jun 24, 2015·American Journal of Respiratory Cell and Molecular Biology·Wei LuoKe Hao
Aug 21, 2015·Science Translational Medicine·David F ChoyPeter Bradding
Oct 17, 2015·American Journal of Respiratory and Critical Care Medicine·Jessie Nicodemus-JohnsonCarole Ober
Dec 31, 2016·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·D RobinsonP Nair
Apr 30, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shi PanDeepak A Deshpande
Jun 28, 2017·Current Protocols in Bioinformatics·Sidra Ahsan, Sorin Drăghici
Oct 31, 2017·Nature Genetics·Manuel A FerreiraLavinia Paternoster
Feb 17, 2018·The European Respiratory Journal·Mark M PerryIan M Adcock
Mar 3, 2018·The Lancet. Respiratory Medicine·Cheng-Jian XuGerard H Koppelman
Aug 8, 2018·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Qijun YuXiaoning Zeng

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Citations

Jun 8, 2021·The Journal of Allergy and Clinical Immunology·Blanca Camoretti-Mercado, Richard F Lockey
Jun 15, 2021·Current Osteoporosis Reports·Abdullah Abood, Charles R Farber

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Methods Mentioned

BETA
genotyping
GTPases

Software Mentioned

IPA
GARFIELD
GEMMA
minimac3
limma
R
MACH
mashr

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