TY - JOUR

T1 - Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology

AU - Schnurr, Theresia Maria

AU - Gjesing, Anette Marianne Prior

AU - Sandholt, Camilla Helene

AU - Jonsson, Anna Elisabet

AU - Mahendran, Yuvaraj

AU - Have, Christian Theil

AU - Ekstrøm, Claus Thorn

AU - Bjerregaard, Anne-Louise

AU - Brage, Søren

AU - Witte, Daniel

AU - Jørgensen, Marit Eika

AU - Aadahl, Mette

AU - Thuesen, Betina Heinsbæk

AU - Linneberg, Allan René

AU - Eiberg, Hans Rudolf Lytchoff

AU - Pedersen, Oluf Borbye

AU - Grarup, Niels

AU - Oskari Kilpeläinen, Tuomas

AU - Hansen, Torben

PY - 2016/11/15

Y1 - 2016/11/15

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0166738

DO - 10.1371/journal.pone.0166738

M3 - Journal article

VL - 11

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e0166738

ER -