体脂百分比与心肺适能之间的遗传相关性提示存在共同的遗传病因。
Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology.
作者信息
Schnurr Theresia M, Gjesing Anette P, Sandholt Camilla H, Jonsson Anna, Mahendran Yuvaraj, Have Christian T, Ekstrøm Claus T, Bjerregaard Anne-Louise, Brage Soren, Witte Daniel R, Jørgensen Marit E, Aadahl Mette, Thuesen Betina H, Linneberg Allan, Eiberg Hans, Pedersen Oluf, Grarup Niels, Kilpeläinen Tuomas O, Hansen Torben
机构信息
Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
出版信息
PLoS One. 2016 Nov 15;11(11):e0166738. doi: 10.1371/journal.pone.0166738. eCollection 2016.
OBJECTIVES
It has long been discussed whether fitness or fatness is a more important determinant of health status. If the same genetic factors that promote body fat percentage (body fat%) are related to cardiorespiratory fitness (CRF), part of the concurrent associations with health outcomes could reflect a common genetic origin. In this study we aimed to 1) examine genetic correlations between body fat% and CRF; 2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and 3) examine whether the fat mass and obesity associated (FTO) locus associates with CRF.
METHODS
Genetic correlations based on pedigree information were examined in a family based cohort (n = 230 from 55 families). For the genetic association analyses, we examined two Danish population-based cohorts (ntotal = 3206). The body fat% GRS was created by summing the alleles of twelve independent risk variants known to associate with body fat%. We assessed CRF as maximal oxygen uptake expressed in millilitres of oxygen uptake per kg of body mass (VO2max), per kg fat-free mass (VO2maxFFM), or per kg fat mass (VO2maxFM). All analyses were adjusted for age and sex, and when relevant, for body composition.
RESULTS
We found a significant negative genetic correlation between VO2max and body fat% (ρG = -0.72 (SE ±0.13)). The body fat% GRS associated with decreased VO2max (β = -0.15 mL/kg/min per allele, p = 0.0034, age and sex adjusted). The body fat%-increasing FTO allele was associated with a 0.42 mL/kg/min unit decrease in VO2max per allele (p = 0.0092, age and sex adjusted). Both associations were abolished after additional adjustment for body fat%. The fat% increasing GRS and FTO risk allele were associated with decreased VO2maxFM but not with VO2maxFFM.
CONCLUSIONS
Our findings suggest a shared genetic etiology between whole body fat% and CRF.
目的
长期以来一直在讨论健康状况的更重要决定因素是健康还是肥胖。如果促进体脂百分比（体脂%）的相同遗传因素与心肺适能（CRF）相关，那么与健康结果的部分并发关联可能反映了共同的遗传起源。在本研究中，我们旨在：1）检查体脂%与CRF之间的遗传相关性；2）确定CRF是否可归因于基于已知体脂%增加位点的遗传风险评分（GRS）；3）检查脂肪量和肥胖相关（FTO）位点是否与CRF相关。
方法
在一个基于家庭的队列（来自55个家庭的230人）中，根据家系信息检查遗传相关性。对于遗传关联分析，我们检查了两个基于丹麦人群的队列（共3206人）。体脂% GRS通过将已知与体脂%相关的12个独立风险变异的等位基因相加来创建。我们将CRF评估为以每千克体重的摄氧量毫升数（最大摄氧量，VO2max）、每千克去脂体重（VO2maxFFM）或每千克脂肪量（VO2maxFM）表示的最大摄氧量。所有分析均针对年龄和性别进行了调整，并在相关时针对身体成分进行了调整。
结果
我们发现VO2max与体脂%之间存在显著的负遗传相关性（ρG = -0.72（标准误±0.13））。体脂% GRS与VO2max降低相关（β = -0.15 mL/kg/min/等位基因，p = 0.0034，年龄和性别调整后）。增加体脂%的FTO等位基因与VO2max每等位基因降低0.42 mL/kg/min单位相关（p = 0.0092，年龄和性别调整后）。在对体脂%进行额外调整后，这两种关联均被消除。增加脂肪%的GRS和FTO风险等位基因与VO2maxFM降低相关，但与VO2maxFFM无关。
结论
我们的研究结果表明全身脂肪%与CRF之间存在共同的遗传病因。
Zotero 插件