Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism

<h3>Background</h3><p dir="ltr">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 o...

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Main Author: Fatima Al-Khelaifi (4741026) (author)
Other Authors: Noha A. Yousri (1392577) (author), Ilhame Diboun (3522413) (author), Ekaterina A. Semenova (8977838) (author), Elena S. Kostryukova (7312016) (author), Nikolay A. Kulemin (8977841) (author), Oleg V. Borisov (1584487) (author), Liliya B. Andryushchenko (8977844) (author), Andrey K. Larin (7311980) (author), Edward V. Generozov (8977847) (author), Eri Miyamoto-Mikami (545704) (author), Haruka Murakami (2177350) (author), Hirofumi Zempo (702019) (author), Motohiko Miyachi (398658) (author), Mizuki Takaragawa (8977850) (author), Hiroshi Kumagai (2571265) (author), Hisashi Naito (769563) (author), Noriyuki Fuku (136826) (author), David Abraham (36404) (author), Aroon Hingorani (256127) (author), Francesco Donati (4741020) (author), Francesco Botrè (4741056) (author), Costas Georgakopoulos (4741032) (author), Karsten Suhre (67967) (author), Ildus I. Ahmetov (8977853) (author), Omar Albagha (8977856) (author), Mohamed A. Elrayess (7956179) (author)
Published: 2020
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author Fatima Al-Khelaifi (4741026)
author2 Noha A. Yousri (1392577)
Ilhame Diboun (3522413)
Ekaterina A. Semenova (8977838)
Elena S. Kostryukova (7312016)
Nikolay A. Kulemin (8977841)
Oleg V. Borisov (1584487)
Liliya B. Andryushchenko (8977844)
Andrey K. Larin (7311980)
Edward V. Generozov (8977847)
Eri Miyamoto-Mikami (545704)
Haruka Murakami (2177350)
Hirofumi Zempo (702019)
Motohiko Miyachi (398658)
Mizuki Takaragawa (8977850)
Hiroshi Kumagai (2571265)
Hisashi Naito (769563)
Noriyuki Fuku (136826)
David Abraham (36404)
Aroon Hingorani (256127)
Francesco Donati (4741020)
Francesco Botrè (4741056)
Costas Georgakopoulos (4741032)
Karsten Suhre (67967)
Ildus I. Ahmetov (8977853)
Omar Albagha (8977856)
Mohamed A. Elrayess (7956179)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Fatima Al-Khelaifi (4741026)
Noha A. Yousri (1392577)
Ilhame Diboun (3522413)
Ekaterina A. Semenova (8977838)
Elena S. Kostryukova (7312016)
Nikolay A. Kulemin (8977841)
Oleg V. Borisov (1584487)
Liliya B. Andryushchenko (8977844)
Andrey K. Larin (7311980)
Edward V. Generozov (8977847)
Eri Miyamoto-Mikami (545704)
Haruka Murakami (2177350)
Hirofumi Zempo (702019)
Motohiko Miyachi (398658)
Mizuki Takaragawa (8977850)
Hiroshi Kumagai (2571265)
Hisashi Naito (769563)
Noriyuki Fuku (136826)
David Abraham (36404)
Aroon Hingorani (256127)
Francesco Donati (4741020)
Francesco Botrè (4741056)
Costas Georgakopoulos (4741032)
Karsten Suhre (67967)
Ildus I. Ahmetov (8977853)
Omar Albagha (8977856)
Mohamed A. Elrayess (7956179)
author_role author
dc.creator.none.fl_str_mv Fatima Al-Khelaifi (4741026)
Noha A. Yousri (1392577)
Ilhame Diboun (3522413)
Ekaterina A. Semenova (8977838)
Elena S. Kostryukova (7312016)
Nikolay A. Kulemin (8977841)
Oleg V. Borisov (1584487)
Liliya B. Andryushchenko (8977844)
Andrey K. Larin (7311980)
Edward V. Generozov (8977847)
Eri Miyamoto-Mikami (545704)
Haruka Murakami (2177350)
Hirofumi Zempo (702019)
Motohiko Miyachi (398658)
Mizuki Takaragawa (8977850)
Hiroshi Kumagai (2571265)
Hisashi Naito (769563)
Noriyuki Fuku (136826)
David Abraham (36404)
Aroon Hingorani (256127)
Francesco Donati (4741020)
Francesco Botrè (4741056)
Costas Georgakopoulos (4741032)
Karsten Suhre (67967)
Ildus I. Ahmetov (8977853)
Omar Albagha (8977856)
Mohamed A. Elrayess (7956179)
dc.date.none.fl_str_mv 2020-06-16T09:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fgene.2020.00595
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Genome-Wide_Association_Study_Reveals_a_Novel_Association_Between_MYBPC3_Gene_Polymorphism_Endurance_Athlete_Status_Aerobic_Capacity_and_Steroid_Metabolism/26176843
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Health sciences
Sports science and exercise
GWAS
SNP
metabolomics
metabolites
elite athletes
endurance
dc.title.none.fl_str_mv Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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 (<i>n</i> = 662) and low/moderate (<i>n </i>= 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 (<i>MYBPC3</i>; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (<i>P</i> = 1.43 × 10<sup>−8</sup>, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO<sub>2</sub><sub>max</sub> than carriers of the AA + AG (<i>P</i> = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10<sup>–05</sup>) including the testosterone precursor androstenediol (3beta,17beta) disulfate.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2020.00595" target="_blank">https://dx.doi.org/10.3389/fgene.2020.00595</a></p>
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oai_identifier_str oai:figshare.com:article/26176843
publishDate 2020
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spelling Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid MetabolismFatima Al-Khelaifi (4741026)Noha A. Yousri (1392577)Ilhame Diboun (3522413)Ekaterina A. Semenova (8977838)Elena S. Kostryukova (7312016)Nikolay A. Kulemin (8977841)Oleg V. Borisov (1584487)Liliya B. Andryushchenko (8977844)Andrey K. Larin (7311980)Edward V. Generozov (8977847)Eri Miyamoto-Mikami (545704)Haruka Murakami (2177350)Hirofumi Zempo (702019)Motohiko Miyachi (398658)Mizuki Takaragawa (8977850)Hiroshi Kumagai (2571265)Hisashi Naito (769563)Noriyuki Fuku (136826)David Abraham (36404)Aroon Hingorani (256127)Francesco Donati (4741020)Francesco Botrè (4741056)Costas Georgakopoulos (4741032)Karsten Suhre (67967)Ildus I. Ahmetov (8977853)Omar Albagha (8977856)Mohamed A. Elrayess (7956179)Biological sciencesGeneticsBiomedical and clinical sciencesMedical biochemistry and metabolomicsHealth sciencesSports science and exerciseGWASSNPmetabolomicsmetaboliteselite athletesendurance<h3>Background</h3><p dir="ltr">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.</p><h3>Results</h3><p dir="ltr">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 (<i>n</i> = 662) and low/moderate (<i>n </i>= 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 (<i>MYBPC3</i>; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status (<i>P</i> = 1.43 × 10<sup>−8</sup>, odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO<sub>2</sub><sub>max</sub> than carriers of the AA + AG (<i>P</i> = 0.005). Subsequent metabolomics analysis revealed several amino acids and lipids associated with rs1052373 G allele (1.82 × 10<sup>–05</sup>) including the testosterone precursor androstenediol (3beta,17beta) disulfate.</p><h3>Conclusions</h3><p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2020.00595" target="_blank">https://dx.doi.org/10.3389/fgene.2020.00595</a></p>2020-06-16T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fgene.2020.00595https://figshare.com/articles/journal_contribution/Genome-Wide_Association_Study_Reveals_a_Novel_Association_Between_MYBPC3_Gene_Polymorphism_Endurance_Athlete_Status_Aerobic_Capacity_and_Steroid_Metabolism/26176843CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261768432020-06-16T09:00:00Z
spellingShingle Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
Fatima Al-Khelaifi (4741026)
Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Health sciences
Sports science and exercise
GWAS
SNP
metabolomics
metabolites
elite athletes
endurance
status_str publishedVersion
title Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
title_full Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
title_fullStr Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
title_full_unstemmed Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
title_short Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
title_sort Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism
topic Biological sciences
Genetics
Biomedical and clinical sciences
Medical biochemistry and metabolomics
Health sciences
Sports science and exercise
GWAS
SNP
metabolomics
metabolites
elite athletes
endurance