Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank

Abstract 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 identi...

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Autores principales:	Emmi Tikkanen, Stefan Gustafsson, David Amar, Anna Shcherbina, Daryl Waggott, Euan A. Ashley, Erik Ingelsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bf66095c61b4c51a9330c0ef93d28da
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spelling	oai:doaj.org-article:3bf66095c61b4c51a9330c0ef93d28da2021-12-02T15:08:53ZBiological Insights Into Muscular Strength: Genetic Findings in the UK Biobank10.1038/s41598-018-24735-y2045-2322https://doaj.org/article/3bf66095c61b4c51a9330c0ef93d28da2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24735-yhttps://doaj.org/toc/2045-2322Abstract 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.Emmi TikkanenStefan GustafssonDavid AmarAnna ShcherbinaDaryl WaggottEuan A. AshleyErik IngelssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emmi Tikkanen Stefan Gustafsson David Amar Anna Shcherbina Daryl Waggott Euan A. Ashley Erik Ingelsson Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
description	Abstract 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.
format	article
author	Emmi Tikkanen Stefan Gustafsson David Amar Anna Shcherbina Daryl Waggott Euan A. Ashley Erik Ingelsson
author_facet	Emmi Tikkanen Stefan Gustafsson David Amar Anna Shcherbina Daryl Waggott Euan A. Ashley Erik Ingelsson
author_sort	Emmi Tikkanen
title	Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
title_short	Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
title_full	Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
title_fullStr	Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
title_full_unstemmed	Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank
title_sort	biological insights into muscular strength: genetic findings in the uk biobank
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3bf66095c61b4c51a9330c0ef93d28da
work_keys_str_mv	AT emmitikkanen biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT stefangustafsson biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT davidamar biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT annashcherbina biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT darylwaggott biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT euanaashley biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank AT erikingelsson biologicalinsightsintomuscularstrengthgeneticfindingsintheukbiobank
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Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank

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