Obesity-related Genetic Variants And Their Associations With Physical Activity

Lee, Harold; Ash, Garrett I.; Angelopoulos, Theodore J.; Gordon, Paul M.; Moyna, Niall M.; Visich, Paul S.; Zoeller, Robert F.; Gordish‐Dressman, Heather; Thompson, Paul D.; Hoffman, Eric P.; Devaney, Joseph M.; Pescatello, Linda S.

doi:10.1249/01.mss.0000476618.67747.71

Cited by 4 publications

(6 citation statements)

References 31 publications

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“…Previous studies have shown that BMI-associated genetic variants are also associated with PA 71 , 72 . Similarly, we found an overall shared genetic basis for PA (especially accelerometer-based measures) with several obesity-related traits (in the expected negative direction of association), suggesting that genetic risk for obesity coincides with genetic propensity for lower PA.…”

Section: Discussionmentioning

confidence: 98%

Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE

et al. 2018

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Background/ObjectivesPhysical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual.Subjects/MethodsWe used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax=377,234) and two measures based on wrist-worn accelerometry data (nmax=91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n=8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA).ResultsWe identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p<5 × 10−9). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer’s risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p<5 × 10−5) with PA across both self-report and accelerometry, including CADM2. We find genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions.ConclusionsThese results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.

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Section: Discussionmentioning

confidence: 98%

Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE

et al. 2018

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“…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. Variants in or close to MC4R was associated with physical activity in three medium quality studies [34,40,42]; however, the GWAS by De Moor et al [28] and Lin et al [31] did not report an association between physical activity and SNPs in the vicinity of the MC4R gene. Online supplementary 6 shows effect size, standard error and p-value for genetic variants from candidate genes studies associated with accelerometry defined phenotypes reported in GWAS summary statistics [26,27].…”

Section: Candidate Gene Studiesmentioning

confidence: 94%

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

Aasdahl

Nilsen

Meisingset

et al. 2021

Int J Behav Nutr Phys Act

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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.

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“…The melanocortin system is composed of arcuate nucleus neurons, which produce pro‐opiomelanocortin (POMC) or agouti‐related peptide (AgRP) and cells that express melanocortin 3 and 4 receptors (MC3R and MC4R) . The melanocortin system receives peripheral influence from leptin produced primarily by adipocytes and ghrelin produced by gastric endocrine cells .…”

Section: Physiological Mechanisms Linking Energy Intake Energy Expenmentioning

confidence: 99%

“…Genetic variations at obesity‐related loci have displayed minor effects on the volume of PA (measured through MET score). Subjects with MC4R (rs17782313) C allele (obesity risk variant) spent 3.5% less MET‐hours/week than those with the TT genotype ( p = 0.02) . Subjects with the TMEM18 obesity risk (T) allele spent 4.1% less MET‐hours/week than those with the CC genotype .…”

Section: Genetics Of Physical Activity and Sedentary Behaviourmentioning

confidence: 99%

Revisiting the evolutionary origins of obesity: lazy versus peppy‐thrifty genotype hypothesis

et al. 2018

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The recent global obesity epidemic is attributed to major societal and environmental changes, such as excessive energy intake and sedentary lifestyle. However, exposure to 'obesogenic' environments does not necessarily result in obesity at the individual level, as 40-75% of body mass index variation in population is attributed to genetic differences. The thrifty genotype theory posits that genetic variants promoting efficient food sequestering and optimal deposition of fat during periods of food abundance were evolutionarily advantageous for the early hunter-gatherer and were positively selected. However, the thrifty genotype is likely too simplistic and fails to provide a justification for the complex distribution of obesity predisposing gene variants and for the broad range of body mass index observed in diverse ethnic groups. This review proposes that gene pleiotropy may better account for the variability in the distribution of obesity susceptibility alleles across modern populations. We outline the lazy-thrifty versus peppy-thrifty genotype hypothesis and detail the body of evidence in the literature in support of this novel concept. Future population genetics and mathematical modelling studies that account for pleiotropy may further improve our understanding of the evolutionary origins of the current obesity epidemic.

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Obesity-related Genetic Variants And Their Associations With Physical Activity

Cited by 4 publications

References 31 publications

Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE

Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE

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

Revisiting the evolutionary origins of obesity: lazy versus peppy‐thrifty genotype hypothesis

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