ZBTB40 和 NFATC1 中的风险变异增加了 IBD 和不良骨骼健康结果的风险，突出了这两种疾病共同的遗传基础。
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.
机构信息
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
出版信息
Inflamm Bowel Dis. 2023 Jun 1;29(6):938-945. doi: 10.1093/ibd/izac273.
BACKGROUND
Inflammatory 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.
METHODS
The study cohort included patients from the Michigan Genomics Initiative. Student's t tests (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.
RESULTS
There 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/m2 vs 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 at P ≤ .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 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).
CONCLUSIONS
Patients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.
背景
炎症性肠病（IBD）与骨质疏松症和骨折风险增加有关。本研究的目的是：（1）确认 IBD 与低骨密度之间的关联；（2）测试跨疾病的共享风险变异。
方法
研究队列包括密歇根基因组倡议的患者。使用学生 t 检验（连续变量）和卡方检验（分类变量）进行单变量分析。多变量逻辑回归用于测试 IBD 对骨质疏松症或骨量减少的影响。使用公开的全基因组关联汇总统计数据来识别改变 IBD 和骨密度风险的变异，并使用孟德尔随机化（MR）来识别遗传预测的 IBD 对骨密度的因果影响。
结果
密歇根基因组倡议队列中有 51405 人，其中 10378 人（20.2%）患有骨质疏松症或骨量减少，1404 人（2.7%）患有 IBD。骨质疏松症或骨量减少患者更可能年龄较大（64 岁比 56 岁；P<0.001）、女性（67%比 49%；P<0.001）、体重指数较低（29kg/m2比 30kg/m2；P<0.001）。使用（比值比，4.60；95%置信区间，3.93-5.37）和未使用（比值比，1.77；95%置信区间，1.42-2.21）类固醇的 IBD 患者骨质疏松症或骨量减少的风险显著增加。有 21 个 IBD 变异与 P≤0.05 时的骨矿物质密度降低相关，有 3 个 IBD 风险变异与 P≤5×10-8 时的骨矿物质密度降低相关。在 3 个全基因组显著变异中，有 2 个增加了 IBD 的风险（rs12568930-T：MIR4418；ZBTB40；rs7236492-C：NFATC1）。MR 未显示遗传预测的 IBD 对骨密度的因果影响（MR Egger，P=0.30；逆方差加权，P=0.63）。
结论
IBD 患者的骨密度降低风险增加，与类固醇的使用无关。ZBTB40 和 NFATC1 中的变异与 IBD 和低骨密度的风险增加有关。
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