Mendelian Randomization and Bayesian Model Averaging of Autoimmune Diseases and Long COVID

Overview

Journal Front Genet

Date 2024 Jul 15

PMID 39005628

Authors

Jieni Feng

Jiankun Chen

Xiaoya Li

Xiaolei Ren

Junxu Chen

Zuming Li

Yuan Wu

Zhongde Zhang

Rongyuan Yang

Jiqiang Li

Yue Lu

Yuntao Liu

Affiliations

Soon will be listed here.

Abstract

Background: Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.

Methods: Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn's disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).

Results: The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00-1.11, = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01-1.19, = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03-1.13, = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.

Conclusion: This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.

References

Shen W, Song Z, Zhong X, Huang M, Shen D, Gao P . Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform. Imeta. 2024; 1(3):e36. PMC: 10989974. DOI: 10.1002/imt2.36. View

Arachchillage D, Rajakaruna I, Pericleous C, Nicolson P, Makris M, Laffan M . Autoimmune disease and COVID-19: a multicentre observational study in the United Kingdom. Rheumatology (Oxford). 2022; 61(12):4643-4655. PMC: 8992350. DOI: 10.1093/rheumatology/keac209. View

Ledford H . Gene linked to long COVID found in analysis of thousands of patients. Nature. 2023; 619(7970):445. DOI: 10.1038/d41586-023-02269-2. View

Efron B . Tweedie's Formula and Selection Bias. J Am Stat Assoc. 2012; 106(496):1602-1614. PMC: 3325056. DOI: 10.1198/jasa.2011.tm11181. View

Simmons D, Nguyen H, Gomez-Rivas E, Jeong Y, Jonsson A, Chen A . SLAMF7 engagement superactivates macrophages in acute and chronic inflammation. Sci Immunol. 2022; 7(68):eabf2846. PMC: 8991457. DOI: 10.1126/sciimmunol.abf2846. View

Pierce B, VanderWeele T . The effect of non-differential measurement error on bias, precision and power in Mendelian randomization studies. Int J Epidemiol. 2012; 41(5):1383-93. DOI: 10.1093/ije/dys141. View

Sin D . Is long COVID an autoimmune disease?. Eur Respir J. 2023; 61(1). DOI: 10.1183/13993003.02272-2022. View

Puel A, Bastard P, Bustamante J, Casanova J . Human autoantibodies underlying infectious diseases. J Exp Med. 2022; 219(4). PMC: 8952682. DOI: 10.1084/jem.20211387. View

Song L, Zhou R, Huang S, Zhou F, Xu S, Wang W . High intestinal and systemic levels of interleukin-23/T-helper 17 pathway in Chinese patients with inflammatory bowel disease. Mediators Inflamm. 2014; 2013:425915. PMC: 3870108. DOI: 10.1155/2013/425915. View

10.

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

11.

Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J . A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017; 36(11):1783-1802. PMC: 5434863. DOI: 10.1002/sim.7221. View

12.

Tursi A, Nenna R . COVID-19 as a Trigger for De Novo Crohn's Disease. Inflamm Bowel Dis. 2022; 28(6):e76-e77. PMC: 8690164. DOI: 10.1093/ibd/izab298. View

13.

Moschen A, Tilg H, Raine T . IL-12, IL-23 and IL-17 in IBD: immunobiology and therapeutic targeting. Nat Rev Gastroenterol Hepatol. 2018; 16(3):185-196. DOI: 10.1038/s41575-018-0084-8. View

14.

Marrack P, Kappler J, Kotzin B . Autoimmune disease: why and where it occurs. Nat Med. 2001; 7(8):899-905. DOI: 10.1038/90935. View

15.

Avrameas S, Selmi C . Natural autoantibodies in the physiology and pathophysiology of the immune system. J Autoimmun. 2013; 41:46-9. DOI: 10.1016/j.jaut.2013.01.006. View

16.

Burgess S, Thompson S . Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017; 32(5):377-389. PMC: 5506233. DOI: 10.1007/s10654-017-0255-x. View

17.

Cayley Jr W . New-Onset Ulcerative Colitis in Patients With COVID-19. Am Fam Physician. 2022; 106(4):362. View

18.

Ceban F, Leber A, Jawad M, Yu M, Lui L, Subramaniapillai M . Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research. Infect Dis (Lond). 2022; 54(7):467-477. PMC: 8935463. DOI: 10.1080/23744235.2022.2043560. View

19.

Vaucher J, Keating B, Lasserre A, Gan W, Lyall D, Ward J . Cannabis use and risk of schizophrenia: a Mendelian randomization study. Mol Psychiatry. 2017; 23(5):1287-1292. PMC: 5984096. DOI: 10.1038/mp.2016.252. View

20.

Hemani G, Zheng J, Elsworth B, Wade K, Haberland V, Baird D . The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018; 7. PMC: 5976434. DOI: 10.7554/eLife.34408. View