医学
现象
单核苷酸多态性
2型糖尿病
内科学
多效性
全基因组关联研究
遗传流行病学
遗传倾向
糖尿病
等位基因
疾病
表型
遗传学
内分泌学
基因型
生物
基因
作者
Vivian Kawai,Mingjian Shi,Ge Liu,Qi Feng,Wei Wei,Cecilia P. Chung,Theresa L. Walunas,Adam J. Gordon,James G. Linneman,Scott J. Hebbring,John B. Harley,Nancy J. Cox,Dan M. Roden,C. Michael Stein,Jonathan D. Mosley
出处
期刊:Lupus
[SAGE]
日期:2021-05-12
卷期号:30 (8): 1264-1272
被引量:1
标识
DOI:10.1177/09612033211014952
摘要
To test the hypothesis that genetic predisposition to systemic lupus erythematosus (SLE) increases the risk of cardiometabolic disorders.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.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.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.
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