Abstract:BackgroundInterleukin‐15 (IL‐15) is a myokine associated with muscle strength, possibly by attenuating protein breakdown. A variant in the alpha‐receptor (IL‐15Rα 1775 A>C, rs2228059) partially modulates the muscle strength and size response to resistance training. We examined if this polymorphism associated with habitual physical activity among European‐American adults.MethodsMen (n = 240, 23.7 ± 0.3 year, body mass index [BMI] 25.3 ± 0.3 kg/m2) and women (n = 292, 23.2 ± 0.3 year, 24.0 ± 0.3 kg/m2) were geno… Show more
“…Among the 48 candidate gene studies, the scores varied from 1 to 9.5, with a median of 6.5. Three candidate gene studies were considered high quality [ 32 , 33 , 41 ], 35 medium quality, while 10 studies were considered low or very low quality.…”
Section: Resultsmentioning
confidence: 99%
“…However, the GWAS by Lin et al [ 31 ] and De Moor et al [ 28 ] did not successfully replicate SNPs in or close to the ACE gene. In another high quality candidate gene study, Bruneau et al [ 33 ] found an association between light intensity physical activity and a SNP in IL15RA (rs2228059). In total, variants in nine candidate genes ( ACE, CASR, CYP19A, FTO, DRD2, CNR1, LEPR, MC4R, NPC1 ) were found to be associated with physical activity or sedentary behaviour in more than one study.…”
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.
“…Among the 48 candidate gene studies, the scores varied from 1 to 9.5, with a median of 6.5. Three candidate gene studies were considered high quality [ 32 , 33 , 41 ], 35 medium quality, while 10 studies were considered low or very low quality.…”
Section: Resultsmentioning
confidence: 99%
“…However, the GWAS by Lin et al [ 31 ] and De Moor et al [ 28 ] did not successfully replicate SNPs in or close to the ACE gene. In another high quality candidate gene study, Bruneau et al [ 33 ] found an association between light intensity physical activity and a SNP in IL15RA (rs2228059). In total, variants in nine candidate genes ( ACE, CASR, CYP19A, FTO, DRD2, CNR1, LEPR, MC4R, NPC1 ) were found to be associated with physical activity or sedentary behaviour in more than one study.…”
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.
“…The PubMed search yielded 902 results, of which 12 studies met the three-inclusion criterion. Two papers [21,22] were added due to appearance in the literature after the initial search. Of the 14 studies, seven were GWAS and seven were candidate gene studies.…”
Section: Resultsmentioning
confidence: 99%
“…The pre-2009 studies that used micro-satellite technology did not provide specific locations for conservation or age predictions and as a result, were dropped from the analysis. After compiling all results, the eight included studies included reported a total of 104 unique SNPs significantly associated with PA [21–29].…”
The purpose of this study was to determine the estimated mutation age and conservation of single-nucleotide polymorphisms (SNPs) associated with physical activity (PA) in humans. All human SNPs found to be significantly associated with PA levels in the literature were cross-referenced with the National Heart, Lung, and Blood Institute’s Grand Opportunity Exome Sequencing Project to find estimated African-American (AA) and European-American (EA) mutation age. As a secondary measure of mutation age, SNPs were searched for in Hawk’s mutation age prediction database which utilizes linkage equilibrium. To determine conservation among hominids, all SNPs were searched in the University of California, Santa Cruz Genome Browser, which contains Neanderthal and chimpanzee reference genomes. Six of the 104 SNPs associated with PA regulation were exon-located missense variants found in
IFNAR2
,
PPARGC1A
,
PML
,
CTBP2
,
IL5RA
, and
APOE
genes. The remaining 98 SNPs were located in non-protein coding regions. Average AA and EA estimated mutation age of the exon-located SNPs were 478.4 ± 327.5 kya and 542.1 ± 369.4 kya, respectively. There were four selective sweeps (suggestive of strong positive selection) of SNPs in humans when compared to Neanderthal or chimpanzee genomes. Exon-located PA candidate SNPs are older than the hypothesized emergence of anatomically modern humans. However, 95% of PA associated SNPs are found in intron and intergenic location. Across all SNPs, there seems to be a high level of conservation of alleles between humans, Neanderthals, and chimpanzees. However, the presence of four selective sweeps suggests there were selection pressures or drift unique to
Homo sapiens
that influenced the development of mutations associated with PA regulation.
“…Following Mackinnon's mediation approach, the direct, indirect, and total effects were estimated using bias‐corrected bootstrap CI (bootstrap = 5000); indirect effects were considered significant if the 95% CI do not contain 0 (Zhao et al., 2010). Weekly physical activity was log‐transformed to reduce the skewness and normalize the distribution based on previous recommendation (Beyler, 2010; Bruneau et al., 2018). Again, probit model with WLSMV was used due to the binary outcome of metabolic syndrome.…”
Financial stress has been linked to an increased risk of metabolic syndrome, yet, it remains unclear whether suboptimal sleep duration and physical inactivity are the adaptive responses to financial stress or effect modifiers in the association between financial stress and metabolic syndrome. Hence, this study aims to examine whether physical activity and sleep duration mediate or moderate the bivariate association between financial stress and metabolic syndrome. A prospective secondary analysis was conducted using data from the Wisconsin Sleep Cohort Study (N = 445, mean[SD] age = 64 [7] years). Baseline moderation effect was examined using subgroup analysis with model constraints; prospective mediation model was examined using bias-corrected bootstrap confidence intervals. Results indicate that participants with higher financial stress were less likely to meet physical activity and sleep recommendations. Baseline moderation analysis indicates that meeting current recommendations of sleep duration and physical activity attenuated the association between financial stress and metabolic syndrome. In the prospective mediation analysis, weekly physical activity levels partially mediated the relationship between financial stress and metabolic syndrome, but sleep duration did not mediate this relationship. In conclusion, the joint effect of optimal sleep duration and physical activity disassociates financial stress from the risk of metabolic syndrome. Future interventions addressing metabolic risk might achieve better outcomes if clinicians and researchers factor in the behavioral adaptation of physical inactivity in financially stressed adults (Clinical Trial Registration: NCT00005557).
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