TY - JOUR
T1 - Gene-respiratory disease interactions for rheumatoid arthritis risk
AU - Kronzer, Vanessa L.
AU - Hayashi, Keigo
AU - Crowson, Cynthia S.
AU - Davis, John M.
AU - McDermott, Gregory C.
AU - Cui, Jing
AU - Losina, Elena
AU - Juge, Pierre Antoine
AU - Cerhan, James R.
AU - Sparks, Jeffrey A.
N1 - Publisher Copyright:
© 2023
PY - 2023/12
Y1 - 2023/12
N2 - Objective: We aimed to identify gene by respiratory tract disease interactions that increase RA risk. Methods: In this case-control study using the Mass General Brigham Biobank, we matched incident RA cases, confirmed by ACR/EULAR criteria, to four controls on age, sex, and electronic health record history. Genetic exposures included a validated overall genetic risk score (GRS) for RA, a Human Leukocyte Antigen (HLA) GRS for RA, and the MUC5B promoter variant, an established risk factor for RA-associated interstitial lung disease (ILD). Preceding respiratory tract diseases came from diagnosis codes (positive predictive value 86%). We estimated attributable proportions (AP) and multiplicative odds ratios (OR) with 95% confidence intervals (CI) for RA for each genetic and respiratory exposure using conditional logistic regression models, adjusting for potential confounders. Results: We identified 653 incident RA cases and 2,607 matched controls (mean 54 years, 76% female). The highest tertile of the overall GRS and the HLA GRS were both associated with increased RA risk (OR 2.28, 95% CI 1.89,2.74; OR 2.02, 95% CI 1.67–2.45). ILD and the HLA GRS exhibited a synergistic relationship for RA risk (OR for both exposures 4.30, 95% CI 1.28,14.38; AP 0.51, 95% CI-0.16,1.18). Asthma and the MUC5B promoter variant also exhibited a synergistic interaction for seropositive RA (OR for both exposures 2.58, 95% CI 1.10,6.07; AP 0.62, 95% CI 0.24,1.00). Conclusion: ILD-HLA GRS and asthma-MUC5B promoter variant showed synergistic interactions for RA risk. Such interactions may prove useful for RA prevention and screening.
AB - Objective: We aimed to identify gene by respiratory tract disease interactions that increase RA risk. Methods: In this case-control study using the Mass General Brigham Biobank, we matched incident RA cases, confirmed by ACR/EULAR criteria, to four controls on age, sex, and electronic health record history. Genetic exposures included a validated overall genetic risk score (GRS) for RA, a Human Leukocyte Antigen (HLA) GRS for RA, and the MUC5B promoter variant, an established risk factor for RA-associated interstitial lung disease (ILD). Preceding respiratory tract diseases came from diagnosis codes (positive predictive value 86%). We estimated attributable proportions (AP) and multiplicative odds ratios (OR) with 95% confidence intervals (CI) for RA for each genetic and respiratory exposure using conditional logistic regression models, adjusting for potential confounders. Results: We identified 653 incident RA cases and 2,607 matched controls (mean 54 years, 76% female). The highest tertile of the overall GRS and the HLA GRS were both associated with increased RA risk (OR 2.28, 95% CI 1.89,2.74; OR 2.02, 95% CI 1.67–2.45). ILD and the HLA GRS exhibited a synergistic relationship for RA risk (OR for both exposures 4.30, 95% CI 1.28,14.38; AP 0.51, 95% CI-0.16,1.18). Asthma and the MUC5B promoter variant also exhibited a synergistic interaction for seropositive RA (OR for both exposures 2.58, 95% CI 1.10,6.07; AP 0.62, 95% CI 0.24,1.00). Conclusion: ILD-HLA GRS and asthma-MUC5B promoter variant showed synergistic interactions for RA risk. Such interactions may prove useful for RA prevention and screening.
KW - Epidemiology
KW - Genetics, MUC5B
KW - Interaction
KW - Respiratory disease
KW - Respiratory tract diseases
KW - Rheumatoid arthritis
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U2 - 10.1016/j.semarthrit.2023.152254
DO - 10.1016/j.semarthrit.2023.152254
M3 - Article
C2 - 37595508
AN - SCOPUS:85168010044
SN - 0049-0172
VL - 63
JO - Seminars in Arthritis and Rheumatism
JF - Seminars in Arthritis and Rheumatism
M1 - 152254
ER -