METHODS: Single nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis.
RESULTS: The meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I2, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions.
CONCLUSIONS: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.
方法:3-羟基-3-甲基戊二酰辅因子A还原酶(HMGCR)和PCSK9的单核苷酸多态性(SNP)从可用的欧洲家系在线数据库中收集。四项与骨质疏松症相关的全基因组关联研究(GWAS)数据作为主要结果,和冠状动脉疾病(CAD)作为药物靶向MR分析的阳性对照。通过敏感性分析检查的MR分析结果纳入meta分析,以检查PCSK9和HMGCR抑制剂与骨质疏松症之间的因果关系。
结果:荟萃分析共涉及1,263,102名受试者,表明PCSK9抑制剂可增加骨质疏松风险(P<0.05,I2,39%)。然而,HMGCR抑制剂与骨质疏松症风险无关。此外,使用另一个与暴露相关的GWAS数据集进行了分析的复制,这导致了类似的结论。
结论:PCSK9抑制剂增加骨质疏松风险。然而,HMGCR抑制剂与骨质疏松症无显著关联。