Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.
Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.
复制标题
DOI：
10.1038/s41598-018-24735-y
复制
发表时间：
2018-04-24
影响因子：
4.6
通讯作者：
Ingelsson E
中科院分区：
文献类型：
--
作者：
Tikkanen E;Gustafsson S;Amar D;Shcherbina A;Waggott D;Ashley EA;Ingelsson E
我们进行了一项大型全基因组关联研究，以发现与肌肉力量相关的遗传变异，并评估肌肉力量对几个健康指标的共同遗传病因学和因果影响。在对223,315名个体的发现分析中，我们确定了101个与握力相关的基因座(P <；5 × 10−8)。其中，在复制数据集(N 111,610)中也被关联(P <； = 0.01和方向一致)。EQTL分析强调了几个已知在神经发育障碍或大脑功能中发挥作用的基因，荟萃分析的结果显示，大脑相关转录本的基因表达显著丰富。此外，我们观察到握力与心脏代谢特征呈负遗传相关，与父母死亡年龄和受教育程度呈正相关。我们还表明，握力与包括认知表现分数在内的脆弱指标具有共同的生物学途径。通过孟德尔随机化，我们提供了证据，较高的握力对冠心病(OR = 0.69，95%CI 0.60~0.79，P <； 0.0001)和房颤(OR = 0.75，95%CI 0.62~0.90，P = 0.003)都有保护作用。总而言之，我们的结果表明握力与心脏代谢和认知健康之间存在共同的遗传病因；并表明保持肌肉力量可以预防未来的心血管事件。
We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength (P <5 × 10−8). Of these, 64 were associated (P < 0.01 and consistent direction) also in the replication dataset (N = 111,610). eQTL analyses highlighted several genes known to play a role in neuro-developmental disorders or brain function, and the results from meta-analysis showed a significant enrichment of gene expression of brain-related transcripts. Further, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents’ age of death and education. We also showed that grip strength had shared biological pathways with indicators of frailty, including cognitive performance scores. By use of Mendelian randomization, we provide evidence that higher grip strength is protective of both coronary heart disease (OR = 0.69, 95% CI 0.60–0.79, P < 0.0001) and atrial fibrillation (OR = 0.75, 95% CI 0.62–0.90, P = 0.003). In conclusion, our results show shared genetic aetiology between grip strength, and cardiometabolic and cognitive health; and suggest that maintaining muscular strength could prevent future cardiovascular events.