Data_Sheet_1_Assessment of causal associations between handgrip strength and cardiovascular diseases: A two sample mendelian randomization study.docx

BackgroundSeveral observational studies have identified that handgrip strength was inversely associated with cardiovascular diseases (CVDs). Nevertheless, causality remains controversial. We conducted Mendelian randomization (MR) analysis to examine whether handgrip strength and risk of CVDs are causally associated.
MethodsWe identified 160 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength and 136 independent SNPs for left-hand grip strength at the genome-wide significant threshold (P < 5 × 10−8) from UK Biobank participants and evaluated these in relation to risk of CVDs. MR estimates was calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analysis was further conducted.
ResultsGenetical liability to handgrip strength was significantly associated with coronary artery disease (CAD) and myocardial infarction (MI), but not stroke, hypertension, or heart failure. Additionally, there was significant association between right-hand grip strength and atrial fibrillation (OR, 0.967; 95% CI, 0.950–0.984; p = 0.000222), however, suggestive significance was found between left-hand grip strength and atrial fibrillation (OR, 0.977; 95% CI, 0.957–0.998; p = 0.033). Results were similar in several sensitivity analysis.
ConclusionOur study provides support at the genetic level that handgrip strength is negatively associated with the risk of CAD, MI, and atrial fibrillation. Specific handgrip strength interventions on CVDs warrant exploration as potential CVDs prevention measures.

研究背景：多项观察性研究已证实，握力与心血管疾病（cardiovascular diseases, CVDs）呈负相关。然而，二者之间的因果关联仍存在争议。本研究采用孟德尔随机化（Mendelian randomization, MR）分析方法，探究握力与心血管疾病发病风险是否存在因果关联。
研究方法：本研究从英国生物银行（UK Biobank）的参与者中，筛选出全基因组显著性阈值（P < 5 × 10^−8）下与右手握力相关的160个独立单核苷酸多态性（single nucleotide polymorphisms, SNPs），以及与左手握力相关的136个独立单核苷酸多态性，并评估这些位点与心血管疾病发病风险的关联。本研究采用逆方差加权（inverse-variance weighted, IVW）法计算MR效应估计值，并开展了多项敏感性分析。
研究结果：握力的遗传易感性与冠状动脉疾病（coronary artery disease, CAD）及心肌梗死（myocardial infarction, MI）存在显著关联，但与脑卒中、高血压或心力衰竭无显著关联。此外，右手握力与心房颤动存在显著关联（比值比OR=0.967，95%置信区间CI=0.950~0.984，P=0.000222）；而左手握力与心房颤动则呈现提示性显著关联（OR=0.977，95%CI=0.957~0.998，P=0.033）。多项敏感性分析得到了一致的研究结果。
研究结论：本研究从遗传层面证实，握力与冠状动脉疾病（CAD）、心肌梗死（MI）及心房颤动的发病风险呈负相关。针对握力的心血管疾病干预策略有望作为潜在的心血管疾病预防手段，值得进一步探索。