title: Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology.
abstract: OBJECTIVE
  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.
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Theresia M
authors.identifier: http://orcid.org/0000-0002-6573-4959
authors.initials: TM
authors.lastname: Schnurr
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anette P
authors.initials: AP
authors.lastname: Gjesing
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Sandholt
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Jonsson
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yuvaraj
authors.initials: Y
authors.lastname: Mahendran
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Have
authors.affiliation: Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus T
authors.initials: CT
authors.lastname: Ekstrøm
authors.affiliation: Section of General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Bjerregaard
authors.affiliation: Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.affiliation: Section of General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.affiliation: National Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Marit E
authors.initials: ME
authors.lastname: Jørgensen
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Aadahl
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen, Denmark.
authors.forename: Betina H
authors.initials: BH
authors.lastname: Thuesen
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen, Denmark.|Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tuomas O
authors.initials: TO
authors.lastname: Kilpeläinen
authors.affiliation: Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology; D000328:Adult; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight; D000072599:Cardiorespiratory Fitness; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010101:Oxygen Consumption / Q000235:genetics