Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.
Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.
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DOI：
10.1001/jamanetworkopen.2023.43290
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发表时间：
2023-11-01
影响因子：
13.8
通讯作者：
Hung, Adriana M.
中科院分区：
文献类型：
--
作者：
Triozzi, Jefferson L.;Hsi, Ryan S.;Wang, Guanchao;Akwo, Elvis A.;Wheless, Lee;Chen, Hua-Chang;Tao, Ran;Ikizler, T. Alp;Robinson-Cohen, Cassianne;Hung, Adriana M.
噻嗪类利尿剂与肾结石风险降低相关吗？在这项多达1079657名成人的遗传关联研究中，噻嗪类利尿剂的遗传代理与统计学显著降低15%的肾结石几率相关。这些结果表明，遗传代理的噻嗪类利尿剂估计长期药物的影响，这一发现支持使用噻嗪类利尿剂预防肾结石。这项遗传关联研究包括美国和欧洲成人的全基因组关联研究汇总统计，使用孟德尔随机化分析来检查噻嗪类利尿剂的遗传代理与肾结石风险的关联。临床试验数据对噻嗪类利尿剂预防肾结石的有效性提出了质疑。确定噻嗪类利尿剂的遗传代理与肾结石风险之间是否存在关联。这项遗传关联研究对全基因组关联研究汇总统计量的衍生暴露和结局进行了孟德尔随机化分析。噻嗪类利尿剂的遗传代理来自国际血压联盟。肾结石病例和对照来自百万退伍军人计划，英国生物银行和FinnGen研究。这些横断面设计未报告随访持续时间。数据分析于二零二三年五月进行。噻嗪类利尿剂的遗传代理是与收缩压相关的噻嗪敏感性氯化钠协同转运蛋白基因的遗传变异。β受体阻滞剂和收缩压的遗传代理作为阴性对照。主要结果是肾结石的几率。次要结果是与肾结石治疗相关的血清实验室值。主要分析包括多达1 079 657个个体，包括50 832个肾结石病例和1 028 825个对照。在所有队列的荟萃分析中，噻嗪类利尿剂的遗传代理与肾结石的低风险相关（OR，0.85; 95%CI，0.81-0.89; P <0.001）。β受体阻滞剂（OR，1.02; 95% CI，0.96-1.07; P = .52）和收缩压（OR，1.00; 95% CI，1.00-1.01; P = .49）的遗传代理与肾结石无关。噻嗪类利尿剂的遗传代理与较高的血清钙（β [SE]，0.051 [0.0092]; P < .001）和总胆固醇（β [SE]，0.065 [0.015]; P < .001）相关，但与较低的血清钾（β [SE]，-0.073 [0.022]; P < .001）相关。在这项遗传关联研究中，噻嗪类利尿剂的遗传代理与肾结石风险降低相关。这一发现反映了药物在一生中的作用，不受临床试验有限随访期的限制。
Are thiazide diuretics associated with reduced risk of kidney stones? In this genetic association study of up to 1 079 657 adults, genetic proxies of thiazide diuretics were associated with a statistically significant 15% lower odds of kidney stones. These results suggest that genetic proxies of thiazide diuretics estimate long-term drug effects; this finding supports the use of thiazide diuretics for kidney stone prevention. This genetic association study including genome-wide association study summary statistics of US and European adults uses mendelian randomization analysis to examine the association of genetic proxies of thiazide diuretics with the risk of kidney stones. Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones. To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones. This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023. Genetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of β-blockers and systolic blood pressure served as negative controls. The main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones. The main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P < .001). Genetic proxies of β-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (β [SE], 0.051 [0.0092]; P < .001) and total cholesterol (β [SE], 0.065 [0.015]; P < .001), but lower serum potassium (β [SE], −0.073 [0.022]; P < .001). In this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.
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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
4
作者：
Bolland, M. J.;Ames, R. W.;Reid, I. R.
通讯作者：
Reid, I. R.
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
DOI：
10.1136/bmj.k601
发表时间：
2018-07-12
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Davies NM;Holmes MV;Davey Smith G
通讯作者：
Davey Smith G