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Genetic-informed proteome-wide scan reveals potential causal plasma proteins for idiopathic pulmonary fibrosis
  1. Jiahao Zhu1,
  2. Houpu Liu1,
  3. Rui Gao1,
  4. Ruicheng Gong1,
  5. Jing Wang1,
  6. Dan Zhou2,3,
  7. Min Yu4,
  8. Yingjun Li1
  1. 1 Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
  2. 2 Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China
  3. 3 Vanderbilt University Medical Center, Nashville, Tennessee, USA
  4. 4 Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
  1. Correspondence to Professor Min Yu, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China; myu{at}cdc.zj.cn; Dr Yingjun Li, Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, People's Republic of China; 2016034036{at}hmc.edu.cn

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which there are no reliable biomarkers or disease-modifying drugs. Here, we integrated human genomics and proteomics to investigate the causal associations between 2769 plasma proteins and IPF. Our Mendelian randomisation analysis identified nine proteins associated with IPF, of which three (FUT3, ADAM15 and USP28) were colocalised. ADAM15 emerged as the top candidate, supported by expression quantitative trait locus analysis in both blood and lung tissue. These findings provide novel insights into the aetiology of IPF and offer translational opportunities in response to the clinical challenges of this devastating disease.

  • Idiopathic pulmonary fibrosis

Data availability statement

The GWAS summary statistics from the International IPF Genetics Consortium and Global Biobank Meta-analysis Initiative are available at https://github.com/genomicsITER/PFgenetics and https://www.globalbiobankmeta.org, respectively. The GWAS summary statistics for 2,941 Olink assays and 4,907 SomaScan assays are available at http://ukb-ppp.gwas.eu and https://www.decode.com/summarydata, respectively. The single-cell RNA sequencing data of human lung tissue are available in the Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/ https://www.ncbi.nlm.nih.gov/geo/, under the accession code GSE227136.

https://doi.org/10.1136/thorax-2024-221398

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    Data availability statement

    The GWAS summary statistics from the International IPF Genetics Consortium and Global Biobank Meta-analysis Initiative are available at https://github.com/genomicsITER/PFgenetics and https://www.globalbiobankmeta.org, respectively. The GWAS summary statistics for 2,941 Olink assays and 4,907 SomaScan assays are available at http://ukb-ppp.gwas.eu and https://www.decode.com/summarydata, respectively. The single-cell RNA sequencing data of human lung tissue are available in the Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/ https://www.ncbi.nlm.nih.gov/geo/, under the accession code GSE227136.

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    Footnotes

    • Contributors JZ contributed to the analysis and interpretation of the data and drafting of the manuscript. HL contributed to data analysis and visualisation. DZ contributed to methodology and interpretation of data. YL contributed to conceptualisation and data acquisition. All authors participated in revisions and approved the final version. YL is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding This study was supported by the Key Discipline of Zhejiang Province in Public Health and Preventative Medicine (First Class, Category A), Hangzhou Medical College; Natural Science Foundation of Zhejiang Province (No. LTGY23H260009), China; and Zhejiang Province Key Science and Technology Plan for Medicine and Health (No. WKJ-ZJ-2333).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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