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Obesity-Related Genetic Variants and their Associations with Physical Activity.

ABSTRACT: BACKGROUND:Meta-analysis of genome-wide association studies identified obesity-related genetic variants. Due to the pleiotropic effects of related phenotypes, we tested six of these obesity-related genetic variants for their association with physical activity: fat mass and obesity-associated (FTO)(rs9939609)T>A, potassium channel tetramerization domain containing (KCTD15) (rs11084753)G>A, melanocortin receptor4 (MC4R)(rs17782313)T>C, neuronal growth regulator 1 (NEGR1)(rs2815752)A>G, SH2B adapter protein 1 (SH2B1)(rs7498665)A>G, and transmembrane protein18 (TMEM18)(rs6548238)C>T. METHOD:European-American women (n = 263) and men (n = 229) (23.5 ± 0.3 years, 24.6 ± 0.2 kg/m2) were genotyped and completed the Paffenbarger physical activity Questionnaire. Physical activity volume in metabolic energy equivalents [MET]-hour/week was derived from the summed time spent (hour/week) times the given MET value for vigorous, moderate, and light intensity physical activity, and sitting and sleeping, respectively. Multivariable adjusted [(age, sex, and body mass index (BMI)] linear regression tested associations among genotype (dominant/recessive model) and the log of physical activity volume. RESULT:MC4R (rs17782313)T>C explained 1.1 % (p = 0.02), TMEM18(rs6548238)C>T 1.2 % (p = 0.01), and SH2B1 (rs7498665)A>G 0.6 % (p = 0.08) of the variability in physical activity volume. Subjects with the MC4R C allele spent 3.5 % less MET-hour/week than those with the TT genotype (p = 0.02). Subjects with the TMEM18 T allele spent 4.1 % less MET-hour/week than those with the CC genotype (p = 0.01). Finally, subjects with the SH2B1 GG genotype spent 3.6 % less MET-hour/week than A allele carriers (p = 0.08). CONCLUSION:Our findings suggest a shared genetic influence among some obesity-related gene loci and physical activity phenotypes that should be explored further. Physical activity volume differences by genotype have public health importance equating to 11-13 lb weight difference annually.

SUBMITTER: Lee H

PROVIDER: S-EPMC4607705 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundResearch 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.MethodsWe 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.ResultsFifty-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.ConclusionGWAS 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 registrationProspero CRD42019119456 .

Project description:ImportanceDespite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic variability, increasing risk of obesity.ObjectiveTo use activity, clinical, and genetic data from the All of Us Research Program (AoURP) to explore the association of genetic risk of higher body mass index (BMI) with the level of physical activity needed to reduce incident obesity.Design, setting, and participantsIn this US population-based retrospective cohort study, participants were enrolled in the AoURP between May 1, 2018, and July 1, 2022. Enrollees in the AoURP who were of European ancestry, owned a personal activity tracking device, and did not have obesity up to 6 months into activity tracking were included in the analysis.ExposurePhysical activity expressed as daily step counts and a polygenic risk score (PRS) for BMI, calculated as weight in kilograms divided by height in meters squared.Main outcome and measuresIncident obesity (BMI ≥30).ResultsA total of 3124 participants met inclusion criteria. Among 3051 participants with available data, 2216 (73%) were women, and the median age was 52.7 (IQR, 36.4-62.8) years. The total cohort of 3124 participants walked a median of 8326 (IQR, 6499-10 389) steps/d over a median of 5.4 (IQR, 3.4-7.0) years of personal activity tracking. The incidence of obesity over the study period increased from 13% (101 of 781) to 43% (335 of 781) in the lowest and highest PRS quartiles, respectively (P = 1.0 × 10-20). The BMI PRS demonstrated an 81% increase in obesity risk (P = 3.57 × 10-20) while mean step count demonstrated a 43% reduction (P = 5.30 × 10-12) when comparing the 75th and 25th percentiles, respectively. Individuals with a PRS in the 75th percentile would need to walk a mean of 2280 (95% CI, 1680-3310) more steps per day (11 020 total) than those at the 50th percentile to have a comparable risk of obesity. To have a comparable risk of obesity to individuals at the 25th percentile of PRS, those at the 75th percentile with a baseline BMI of 22 would need to walk an additional 3460 steps/d; with a baseline BMI of 24, an additional 4430 steps/d; with a baseline BMI of 26, an additional 5380 steps/d; and with a baseline BMI of 28, an additional 6350 steps/d.Conclusions and relevanceIn this cohort study, the association between daily step count and obesity risk across genetic background and baseline BMI were quantified. Population-based recommendations may underestimate physical activity needed to prevent obesity among those at high genetic risk.

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Obesity-Related Genetic Variants and their Associations with Physical Activity.

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