Risk Variants in or Near ZBTB40 AND NFATC1 Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases.
Risk Variants in or Near ZBTB40 AND NFATC1 Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases.
复制标题
ZBTB40 和 NFATC1 中或附近的风险变异会增加 IBD 和不良骨骼健康结果的风险，凸显这两种疾病的共同遗传基础。
DOI：
10.1093/ibd/izac273
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发表时间：
2023
影响因子：
4.9
通讯作者：
Speliotes,ElizabethK
中科院分区：
文献类型：
--
作者：
Cushing,KellyC;Chen,Yanhua;Du,Xiaomeng;Chen,Vincent;Kuppa,Annapurna;Higgins,Peter;Speliotes,ElizabethK
BackgroundInflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.MethodsThe study cohort included patients from the Michigan Genomics Initiative. Student’sttests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.ResultsThere were 51 405 individuals in the Michigan Genomics Initiative cohort including 10 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age;P< .001), female (67% vs 49%;P< .001), and have a lower body mass index (29 kg/m2vs 30 kg/m2;P< .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density atP≤ .05 and 3 IBD risk variants associated with reduced bone mineral density atP≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T:MIR4418;ZBTB40; rs7236492-C:NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger,P= .30; inverse variance weighted,P= .63).ConclusionsPatients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or nearZBTB40andNFATC1are associated with an increased risk of IBD and low bone density.
