TY - JOUR
T1 - Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
AU - Al-Khelaifi, Fatima
AU - Yousri, Noha A.
AU - Diboun, Ilhame
AU - Semenova, Ekaterina A.
AU - Kostryukova, Elena S.
AU - Kulemin, Nikolay A.
AU - Borisov, Oleg V.
AU - Andryushchenko, Liliya B.
AU - Larin, Andrey K.
AU - Generozov, Edward V.
AU - Miyamoto-Mikami, Eri
AU - Murakami, Haruka
AU - Zempo, Hirofumi
AU - Miyachi, Motohiko
AU - Takaragawa, Mizuki
AU - Kumagai, Hiroshi
AU - Naito, Hisashi
AU - Fuku, Noriyuki
AU - Abraham, David
AU - Hingorani, Aroon
AU - Donati, Francesco
AU - Botrè, Francesco
AU - Georgakopoulos, Costas
AU - Suhre, Karsten
AU - Ahmetov, Ildus I.
AU - Albagha, Omar
AU - Elrayess, Mohamed A.
N1 - Funding Information:
Authors would like to thank Qatar National Research Fund (QNRF) for funding this project. Grant number NPRP7-272-1-041 (ME, KS, CG, and FB). An earlier version of this manuscript has been released as a pre-print at [ResearchSqure], (Fatima et al., 2019). Funding. This study was funded by Qatar National Research Fund (QNRF), Grant number NPRP7-272-1-041 (ME, KS, CG, and FB). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher Copyright:
© Copyright © 2020 Al-Khelaifi, Yousri, Diboun, Semenova, Kostryukova, Kulemin, Borisov, Andryushchenko, Larin, Generozov, Miyamoto-Mikami, Murakami, Zempo, Miyachi, Takaragawa, Kumagai, Naito, Fuku, Abraham, Hingorani, Donati, Botrè, Georgakopoulos, Suhre, Ahmetov, Albagha and Elrayess.
PY - 2020/6/16
Y1 - 2020/6/16
N2 - Background: The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n = 662) and low/moderate (n = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P = 1.43 × 10−8, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA + AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10–05) including the testosterone precursor androstenediol (3beta,17beta) disulfate. Conclusions: This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
AB - Background: The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high (n = 662) and low/moderate (n = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein (MYBPC3; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (P = 1.43 × 10−8, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO2max than carriers of the AA + AG (P = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10–05) including the testosterone precursor androstenediol (3beta,17beta) disulfate. Conclusions: This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted.
KW - GWAS
KW - SNP
KW - elite athletes
KW - endurance
KW - metabolites
KW - metabolomics
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U2 - 10.3389/fgene.2020.00595
DO - 10.3389/fgene.2020.00595
M3 - Article
AN - SCOPUS:85087125805
SN - 1664-8021
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 595
ER -