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Proteomic associations with forced expiratory volume : a Mendelian randomisation study

Proteomic associations with forced expiratory volume : a Mendelian randomisation study


Title: Proteomic associations with forced expiratory volume : a Mendelian randomisation study
Author: Axelsson, Gisli Thor
Jonmundsson, Thorarinn
Woo, Youngjae
Frick, Elisabet Alexandra
Aspelund, Thor   orcid.org/0000-0002-7998-5433
Loureiro, Joseph J.
Orth, Anthony P.
Jennings, Lori L.
Gudmundsson, Gunnar
Emilsson, Valur   orcid.org/0000-0001-9982-0524
... 2 more authors Show all authors
Date: 2024-12
Language: English
Scope: 1871700
School: Health Sciences
Department: Faculty of Medicine
Interdisciplinary Graduate Studies
Series: Respiratory Research; 25(1)
ISSN: 1465-9921
DOI: 10.1101/2023.06.30.23292035
Subject: Lungnalæknisfræði; Forced expiratory volume; Lung function tests; Mendelian randomisation; Proteomics; Pulmonary and Respiratory Medicine; SDG 3 - Good Health and Well-being
URI: https://hdl.handle.net/20.500.11815/4702

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Citation:

Axelsson , G T , Jonmundsson , T , Woo , Y , Frick , E A , Aspelund , T , Loureiro , J J , Orth , A P , Jennings , L L , Gudmundsson , G , Emilsson , V , Gudmundsdottir , V & Gudnason , V 2024 , ' Proteomic associations with forced expiratory volume : a Mendelian randomisation study ' , Respiratory Research , vol. 25 , no. 1 , 44 . https://doi.org/10.1101/2023.06.30.23292035 , https://doi.org/10.1186/s12931-023-02587-z

Abstract:

Background: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Methods: Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). Results: In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. Conclusions: In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.

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Publisher Copyright: © 2024, The Author(s).

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