title: No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes.
abstract: There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
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authors.forename: Noriyuki
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authors.affiliation: Department of Sport Medicine Humboldt University and Charite University School of Medicine, Berlin, Germany.
authors.forename: Bernd
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authors.lastname: Wolfarth
authors.affiliation: Centre for Sport and Exercise Science and Medicine (SESAME), University of Brighton, Eastbourne, United Kingdom.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.|School of Public Health, University of South Carolina, Columbia, SC, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sarzynski
authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Alexeev
authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.|Sport Technology Research Centre, Volga Region State Academy of Physical Culture, Sport and Tourism, Kazan, Russia.
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authors.initials: II
authors.lastname: Ahmetov
authors.affiliation: Department of Kinesiology, Laval University, Ste-Foy, Québec, Canada.
authors.forename: Marcel R
authors.initials: MR
authors.lastname: Boulay
authors.affiliation: University of Szczecin, Department of Physical Education and Health Promotion, Szczecin, Poland.|Academy of Physical Education and Sport, Department of Tourism and Recreation, Gdansk, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Cieszczyk
authors.affiliation: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Victoria, Australia.
authors.forename: Nir
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authors.affiliation: Pharmacogenomics Laboratory, Institute of Chemical Biology and Fundamental Medicine of SB RAS, Novosibirsk, Russia.|Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Maxim L
authors.initials: ML
authors.lastname: Filipenko
authors.affiliation: Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Victoria, Australia.|Institute of Neuroscience and Muscle Research, Childrens Hospital Westmead, Westmead, Australia.
authors.forename: Fleur C
authors.initials: FC
authors.lastname: Garton
authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Edward V
authors.initials: EV
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authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Vadim M
authors.initials: VM
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authors.affiliation: Pharmacogenomics Laboratory, Institute of Chemical Biology and Fundamental Medicine of SB RAS, Novosibirsk, Russia.|Novosibirsk State University, Novosibirsk, Russia.
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authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
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authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
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authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
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authors.affiliation: University of Szczecin, Department of Physical Education and Health Promotion, Szczecin, Poland.
authors.forename: Agnieszka
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authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan.
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authors.lastname: Miyachi
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authors.forename: Carlos A
authors.initials: CA
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authors.affiliation: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: Haruka
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authors.lastname: Murakami
authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Ospanova
authors.affiliation: College of Medicine, Veterinary & Life Sciences, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: Research Institute for Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Pavlenko
authors.affiliation: Pharmacogenomics Laboratory, Institute of Chemical Biology and Fundamental Medicine of SB RAS, Novosibirsk, Russia.|Novosibirsk State University, Novosibirsk, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Pyankova
authors.affiliation: Universidad Europea and Research Institute i+12, Madrid, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.affiliation: University of Szczecin, Department of Physical Education and Health Promotion, Szczecin, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sawczuk
authors.affiliation: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Scott
authors.affiliation: Federal Medical Biological Agency, Moscow, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Uyba
authors.affiliation: Universidad Europea and Research Institute i+12, Madrid, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.affiliation: Department of Kinesiology, Laval University, Ste-Foy, Québec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Perusse
authors.affiliation: Cardiovascular & Metabolic Disorders Program, and Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Kuopio Research Institute of Exercise Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rauramaa
authors.affiliation: Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Victoria, Australia.|Institute of Neuroscience and Muscle Research, Childrens Hospital Westmead, Westmead, Australia.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.affiliation: Universidad Europea and Research Institute i+12, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
authors.affiliation: Centre for Sport and Exercise Science and Medicine (SESAME), University of Brighton, Eastbourne, United Kingdom.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Pitsiladis
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D000483:Alleles; D056352:Athletes; D056915:DNA Copy Number Variations; D015870:Gene Expression; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D005819:Genetic Markers; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000235:genetics; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics; D010807:Physical Endurance / Q000235:genetics*; D010809:Physical Fitness; D020641:Polymorphism, Single Nucleotide; D057185:Sedentary Behavior; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D005819:Genetic Markers; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase
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