There Are No Lung Diseases…

Although many diseases primarily affect the lungs, most of these diseases also involve other organ systems. Moreover, current diagnostic categories for complex lung diseases include heterogeneous syndromes rather than distinct pathobiological processes. Large-scale genome-wide association studies (GWAS) in many thousands of COPD cases and control subjects have identified more than 80 genomic regions that contain COPD susceptibility genes. Combining statistical fine mapping and open chromatin assays has enabled the identification of some of the functional variants within these GWAS loci. Although genetic association studies have provided important insights into many complex diseases, single genetic variants are unlikely to explain complex diseases, because perturbations of biological networks, not isolated genes, confer disease risk. Using protein-protein interaction network analysis, we have identified a biological connection between two COPD GWAS genes, FAM13A and TGFB2. Different Omics data types provide complementary information about complex diseases. When analyzed within a network context, multiple Omics data has the potential to provide new insights into the pathogenesis and heterogeneity of complex lung diseases.

Content

Author and article information

Conference

Publisher: ScienceOpen

Publication date (Electronic): 17 August 2022

Affiliations

[1 ] Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA

Article

DOI: 10.14293/S2199-rexpo22004.v1

SO-VID: 361d8db1-5cf4-4eb9-8b33-cbb6487b1960

License:

Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

Conference name: RExPO22

Conference location: Maastricht, Netherlands

Conference date: 2-3 September, 2022

History

Data availability: Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Keywords: Network Medicine,COPD,Genome-wide Association Studies,Multiple Omics

References

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Comments

Comment on this article

[1] Duong MyLinh, Islam Shofiqul, Rangarajan Sumathy, Leong Darryl, Kurmi Om, Teo Koon, Killian Kieran, Dagenais Gilles, Lear Scott, Wielgosz Andreas, Nair Sanjeev, Mohan Viswanathan, Mony Prem, Gupta Rajeev, Kumar Rajesh, Rahman Omar, Yusoff Khalid, du Plessis Johannes Lodewykus, Igumbor Ehimario U, Chifamba Jephat, Li Wei, Lu Yin, Zhi Fumin, Yan Ruohua, Iqbal Romaina, Ismail Noorhassim, Zatonska Katarzyna, Karsidag Kubilay, Rosengren Annika, Bahonar Ahmad, Yusufali Afazalhussein, Lamelas Pablo M, Avezum Alvaro, Lopez-Jaramillo Patricio, Lanas Fernando, O'Byrne Paul M, Yusuf Salim. Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study. The Lancet Global Health. Vol. 7(5)2019. Elsevier BV. [Cross Ref]

[2] Silverman Edwin K., Sandhaus Robert A.. Alpha<sub>1</sub>-Antitrypsin Deficiency. New England Journal of Medicine. Vol. 360(26):2749–2757. 2009. Massachusetts Medical Society. [Cross Ref]

[4] Benway Christopher J., Liu Jiangyuan, Guo Feng, Du Fei, Randell Scott H., Cho Michael H., Silverman Edwin K., Zhou Xiaobo. Chromatin Landscapes of Human Lung Cells Predict Potentially Functional Chronic Obstructive Pulmonary Disease Genome-Wide Association Study Variants. American Journal of Respiratory Cell and Molecular Biology. Vol. 65(1):92–102. 2021. American Thoracic Society. [Cross Ref]

[5] Sharma Amitabh, Kitsak Maksim, Cho Michael H., Ameli Asher, Zhou Xiaobo, Jiang Zhiqiang, Crapo James D., Beaty Terri H., Menche Jörg, Bakke Per S., Santolini Marc, Silverman Edwin K.. Integration of Molecular Interactome and Targeted Interaction Analysis to Identify a COPD Disease Network Module. Scientific Reports. Vol. 8(1)2018. Springer Science and Business Media LLC. [Cross Ref]

[6] Gong Lu, Bates Samuel, Li Jian, Qiao Dandi, Glass Kimberly, Wei Wenyi, Hsu Victor W., Zhou Xiaobo, Silverman Edwin K.. Connecting COPD GWAS Genes: FAM13A Controls TGFβ2 Secretion by Modulating AP-3 Transport. American Journal of Respiratory Cell and Molecular Biology. Vol. 65(5):532–543. 2021. American Thoracic Society. [Cross Ref]

[7] Sasaki Haruka, Zhang Yi, Emala Charles W., Mizuta Kentaro. Melatonin MT<sub>2</sub> receptor is expressed and potentiates contraction in human airway smooth muscle. American Journal of Physiology-Lung Cellular and Molecular Physiology. Vol. 321(6)2021. American Physiological Society. [Cross Ref]