金属元素与广泛的临床结果相关。这些关联的现有流行病学证据通常不一致,并且存在混淆和反向因果关系。我们旨在探讨不同血液金属元素水平的广泛临床效果和可能的潜在机制。
我们通过使用金属元素相关的遗传基因座作为工具变量进行了双样本孟德尔随机化(MR)分析,以评估UKBiobank队列中血液金属元素水平与1050疾病结果之间的因果关系。共有408,910名英国白人参与者参加了分析。我们进一步利用金属元素相关基因和疾病相关基因构建了蛋白质-蛋白质相互作用(PPI)网络。
共有8种金属元素与63种疾病有关。值得注意的是,我们在同一疾病的两种不同金属元素之间发现了9对暗示性证据。硒和铅共享一些相关的临床结果,包括糖尿病,2型糖尿病,淋巴样白血病,和急性咽炎.铅和锌共享获得性甲状腺功能减退症的相关疾病。铁和铜共享关节病的相关疾病。铜和锌共享脑动脉闭塞的相关疾病。钙和锌共享关节病的相关疾病。此外,PPI网络在基因水平上提供了金属元素与疾病结局之间的潜在联系.
我们对八种金属元素的MR研究全面表征了它们共同和独特的临床效果。强调它们在多种疾病中的潜在因果作用。鉴于血液金属元素的可修饰性和临床干预的潜力,这些发现值得进一步调查。
Metal elements have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. We aimed to explore the broad clinical effects of varying blood metal element levels and possible underlying mechanisms.
We performed a two-sample Mendelian randomization (MR) analysis by using metal element-associated genetic loci as instrumental variable to evaluate the causal associations between blood metal element levels and 1050 disease outcomes in a UK Biobank cohort. A total of 408,910 White British participants were enrolled in the analysis. We further used the metal element-related genes and disease-related genes to construct a protein-protein interaction (PPI) network.
Eight metal elements were associated with 63 diseases in total. Notably, we found nine pairs of suggestive evidence between two different metal elements for the same disease. Selenium and lead share some of the associated clinical outcomes, including diabetes mellitus, type 2 diabetes, lymphoid leukemia, and acute pharyngitis. Lead and zinc share the associated disease of acquired hypothyroidism. Iron and copper share the associated disease of arthropathies. Copper and zinc share the associated disease of occlusion of cerebral arteries. Calcium and zinc share the associated disease of arthropathies. In addition, the PPI network provided potential links between metal elements and disease outcomes at the genetic level.
Our MR study of eight metal elements comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in multiple diseases. Given the modifiable nature of blood metal elements and the potential for clinical interventions, these findings warrant further investigation.