Genetic Associations Between Smoking- and Glaucoma-Related Traits.
Genetic Associations Between Smoking- and Glaucoma-Related Traits.
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DOI：
10.1167/tvst.12.2.20
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发表时间：
2023-02-01
影响因子：
3
通讯作者：
Pasquale, Louis R
中科院分区：
文献类型：
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作者：
Tran, Jessica H;Stuart, Kelsey V;de Vries, Victor;Vergroesen, Joelle E;Cousins, Clara C;Hysi, Pirro G;Do, Ron;Rocheleau, Ghislain;Kang, Jae H;Wiggs, Janey L;MacGregor, Stuart;Khawaja, Anthony P;Mackey, David A;Klaver, Caroline C W;Ramdas, Wishal D;Pasquale, Louis R
本研究的目的是描述吸烟与青光眼之间的遗传关系。我们使用吸烟开始、吸烟强度（每天吸烟[CPD]）、眼内压（IOP）、垂直杯盘比和开角型青光眼（OAG）的汇总水平遗传数据来估计全局遗传相关性（rg），并进行探索性状之间关系的双样本孟德尔随机化（MR）实验。最后，我们研究了鹿特丹研究参与者的吸烟遗传风险评分（GRS）和吸烟特征与测量的IOP和OAG之间的关联。我们确定了弱逆rg之间的吸烟和肺癌相关的性状，是微不足道的Bonferroni校正后。然而，MR分析显示，遗传预测的吸烟开始与较低的IOP相关（-0.18 mm Hg/SD，95%置信区间[CI] =-0.30至-0.06，P = 0.003）。此外，遗传预测的吸烟强度与OAG风险降低相关（比值比[OR] = 0.74/SD，95%CI = 0.61至0.90，P = 0.002）。在鹿特丹研究中，在多变量校正分析中，开始吸烟的GRS与较低的IOP（-0.09 mmHg/SD，95% CI =-0.17至0.01，P = 0.04）和较低的OAG几率（OR = 0.84/SD，95% CI = 0.73至0.98，P = 0.02）相关。相反，吸烟史和CPD与IOP（P ≥ 0.38）或OAG（P ≥ 0.54）均无关。吸烟强度GRS与青光眼特征之间无相关性（P ≥ 0.13）。从鹿特丹研究参与者产生的MR实验和GRS支持吸烟和青光眼之间的反比关系。了解吸烟和青光眼之间的反向关系的遗传驱动因素可以对青光眼病理生理学产生新的见解。
The purpose of this study was to describe the genetic relationship between smoking and glaucoma. We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (−0.18 mm Hg per SD, 95% confidence interval [CI] = −0.30 to −0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (−0.09 mm Hg per SD, 95% CI = −0.17 to −0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13). MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.