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Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

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Theresia Maria Schnurr, Anette Marianne Prior Gjesing, Camilla Helene Sandholt, Anna Elisabet Jonsson, Yuvaraj Mahendran, Christian Theil Have, Claus Thorn Ekstrøm, Anne-Louise Bjerregaard, Søren Brage, Daniel Witte, Marit Eika Jørgensen, Mette Aadahl, Betina Heinsbæk Thuesen, Allan René Linneberg, Hans Rudolf Lytchoff Eiberg, Oluf Borbye Pedersen, Niels Grarup, Tuomas Oskari Kilpeläinen, Torben Hansen

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.
Original languageEnglish
Article numbere0166738
JournalP L o S One
Issue number11
Number of pages14
StatePublished - 15 Nov 2016

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