Abstract
Objectives: To test the hypothesis that genetic predisposition to systemic lupus erythematosus (SLE) increases the risk of cardiometabolic disorders. Methods: Using 41 single nucleotide polymorphisms (SNPs) associated with SLE, we calculated a weighted genetic risk score (wGRS) for SLE. In a large biobank we tested the association between this wGRS and 9 cardiometabolic phenotypes previously associated with SLE: atrial fibrillation, ischemic stroke, coronary artery disease, type 1 and type 2 diabetes, obesity, chronic kidney disease, hypertension, and hypercholesterolemia. Additionally, we performed a phenome-wide association analysis (pheWAS) to discover novel clinical associations with a genetic predisposition to SLE. Findings were replicated in the Electronic Medical Records and Genomics (eMERGE) Network. To further define the association between SLE-related risk alleles and the selected cardiometabolic phenotypes, we performed an inverse variance weighted regression (IVWR) meta-analysis. Results: The wGRS for SLE was calculated in 74,759 individuals of European ancestry. Among the pre-selected phenotypes, the wGRS was significantly associated with type 1 diabetes (OR [95%CI] =1.11 [1.06, 1.17], P-value = 1.05x10−5). In the PheWAS, the wGRS was associated with several autoimmune phenotypes, kidney disorders, and skin neoplasm; but only the associations with autoimmune phenotypes were replicated. In the IVWR meta-analysis, SLE-related risk alleles were nominally associated with type 1 diabetes (P = 0.048) but the associations were heterogeneous and did not meet the adjusted significance threshold. Conclusion: A weighted GRS for SLE was associated with an increased risk of several autoimmune-related phenotypes including type I diabetes but not with cardiometabolic disorders.
Original language | English (US) |
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Pages (from-to) | 1264-1272 |
Number of pages | 9 |
Journal | Lupus |
Volume | 30 |
Issue number | 8 |
DOIs | |
State | Published - Jul 2021 |
Keywords
- Systemic lupus erythematosus
- genetic risk score
- pleiotropy
ASJC Scopus subject areas
- Rheumatology
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sj-xlsx-1-lup-10.1177_09612033211014952 - Supplemental material for Pleiotropy of systemic lupus erythematosus risk alleles and cardiometabolic disorders: A phenome-wide association study and inverse-variance weighted meta-analysis
Kawai, V. K. (Creator), Shi, M. (Contributor), Liu, G. (Creator), Feng, Q. (Creator), Wei, W. (Creator), Chung, C. P. (Creator), Walunas, T. L. (Creator), Gordon, A. S. (Creator), Linneman, J. G. (Creator), Hebbring, S. J. (Creator), Harley, J. B. (Creator), Cox, N. J. (Creator), Roden, D. M. (Creator), Stein, C. M. (Contributor) & Mosley, J. D. (Creator), SAGE Journals, 2021
DOI: 10.25384/sage.14588139.v1, https://sage.figshare.com/articles/dataset/sj-xlsx-1-lup-10_1177_09612033211014952_-_Supplemental_material_for_Pleiotropy_of_systemic_lupus_erythematosus_risk_alleles_and_cardiometabolic_disorders_A_phenome-wide_association_study_and_inverse-variance_weighted_meta-analysis/14588139/1
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Pleiotropy of systemic lupus erythematosus risk alleles and cardiometabolic disorders: A phenome-wide association study and inverse-variance weighted meta-analysis
Kawai, V. K. (Creator), Shi, M. (Contributor), Liu, G. (Creator), Feng, Q. (Creator), Wei, W. (Creator), Chung, C. P. (Creator), Walunas, T. L. (Creator), Gordon, A. S. (Creator), Linneman, J. G. (Creator), Hebbring, S. J. (Creator), Harley, J. B. (Creator), Cox, N. J. (Creator), Roden, D. M. (Creator), Stein, C. M. (Contributor) & Mosley, J. D. (Creator), SAGE Journals, 2021
DOI: 10.25384/sage.c.5423292.v1, https://sage.figshare.com/collections/Pleiotropy_of_systemic_lupus_erythematosus_risk_alleles_and_cardiometabolic_disorders_A_phenome-wide_association_study_and_inverse-variance_weighted_meta-analysis/5423292/1
Dataset