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.
Causal associations of circulating biomarkers with cardiovascular disease
The overall goal of this project is to study the causal roles of the 36 biomarkers currently being assayed in UK Biobank for development of coronary heart disease, stroke and heart failure. Knowledge about causal relations of these 36 biomarkers with cardiovascular outcomes will give important insights regarding the etiological understanding of these diseases and accelerate development of new prevention strategies, including druggable targets. Hence, the proposed research does meet UK Biobank's stated purpose via improving the prevention and treatment of heart disease and stroke. First, we will study associations of 36 circulating biomarkers representing different biological systems with incidence of coronary heart disease, stroke and heart failure.
Second, by combing data from the UK Biobank gene analyses with the biomarker data, we will perform genetic studies across the whole human genome for all 36 biomarkers to establish common genetic variation associated with respective biomarker.
Third, we will perform so called Mendelian randomization analyses to study whether the biomarkers are causally related to coronary heart disease, stroke and heart failure.
Full cohort (n=502,650).
|Lead investigator:||Professor Themistocles Assimes|
|Lead institution:||Stanford University|
8 related Returns
|Return ID||App ID||Description||Archive Date|
|2167||13721||Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease||9 Apr 2020|
|2792||13721||Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease: Addressing the Barker Hypothesis With Mendelian Randomization||4 Nov 2020|
|2829||13721||Body composition and atrial fibrillation: a Mendelian randomization study||18 Nov 2020|
|2794||13721||Clinical and Genetic Determinants of Varicose Veins||4 Nov 2020|
|2163||13721||Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development||8 Apr 2020|
|2793||13721||Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank||4 Nov 2020|
|2831||13721||Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion||19 Nov 2020|
|2888||13721||Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank||27 Nov 2020|
|2167||Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank||Tikkanen E et al.||2018||Sci Rep|