Genetic variants related to physical activity or sedentary behaviour: a systematic review

Abstract

Background Research shows that part of the variation in physical activity and sedentary behaviour may be explained by genetic factors. Identifying genetic variants associated with physical activity and sedentary behaviour can improve causal inference in physical activity research. The aim of this systematic review was to provide an updated overview of the evidence of genetic variants associated with physical activity or sedentary behaviour. Methods We performed systematic literature searches in PubMed and Embase for studies published from 1990 to April 2020 using keywords relating to “physical activity”, “exercise”, “sedentariness” and “genetics”. Physical activity phenotypes were either based on self-report (e.g., questionnaires, diaries) or objective measures (e.g., accelerometry, pedometer). We considered original studies aiming to i) identify new genetic variants associated with physical activity or sedentary behaviour (i.e., genome wide association studies [GWAS]), or ii) assess the association between known genetic variants and physical activity or sedentary behaviour (i.e., candidate gene studies). Study selection, data extraction, and critical appraisal were carried out by independent researchers, and risk of bias and methodological quality was assessed for all included studies. Results Fifty-four out of 5420 identified records met the inclusion criteria. Six of the included studies were GWAS, whereas 48 used a candidate gene approach. Only one GWAS and three candidate gene studies were considered high-quality. The six GWAS discovered up to 10 single nucleotide polymorphisms (SNPs) associated with physical activity or sedentariness that reached genome-wide significance. In total, the candidate gene studies reported 30 different genes that were associated (p < 0.05) with physical activity or sedentary behaviour. SNPs in or close to nine candidate genes were associated with physical activity or sedentary behaviour in more than one study. Conclusion GWAS have reported up to 10 loci associated with physical activity or sedentary behaviour. Candidate gene studies have pointed to some interesting genetic variants, but few have been replicated. Our review highlights the need for high-quality GWAS in large population-based samples, and with objectively assessed phenotypes, in order to establish robust genetic instruments for physical activity and sedentary behaviour. Furthermore, consistent replications in GWAS are needed to improve credibility of genetic variants. Trial registration Prospero CRD42019119456.

DNA Methylation Analysis of Imprinted Genes in the Cortex and Hippocampus of Cross-Fostered Mice Selectively Bred for Increased Voluntary Wheel-Running

“…Exercise has powerful effects on neurobiological processes such as neurotransmission, cognition, and reward-dependent behaviors (Rhodes et al 2005 ; Caetano-Anolles et al 2016 ; Saul et al 2017 ). While motivation and physiological ability are critical determinants of an individual’s physical activity levels (Garland et al 2017 ), long-term genetic selection experiments in laboratory mice have also illuminated genes associated with elevated levels of voluntary exercise (Kelly et al 2012 ; Kostrzewa and Kas 2014 ; Vellers et al 2018 ; Aasdahl et al 2021 ). RNA (Zhang et al 2018 ) and whole genome (Xu and Garland 2017 ; Hillis et al 2020 ) sequencing from mice selected for elevated physical activity levels have revealed differential expression of genes associated with behavior, motivation, and athletic ability, supporting a genetic basis for elevated physical activity.…”

Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning

“…The precise underlying molecular mechanisms behind these physiological changes remain poorly characterised. It is clear that individual’s inherited genetic variants, epigenetic makeup, and the resultant regulation of gene expression, impacts of PA and PA-related phenotypes as well as the ageing process [ 2 – 5 ].…”

Shared brain and genetic architectures between mental health and physical activity

“…Genetic factors may explain different degrees of variance in physical activity depending on sex 54 and activity duration 55 . GWAS and candidate gene studies have also identified specific genomic loci implicated in physical activity, with a recent GWAS conducted in the UK Biobank identifying 14 independent loci and gene pathways enriched in neurological disease, brain structure, and cognitive function 52,[56][57][58] .…”