TY - JOUR

T1 - Multi-phase, multi-ethnic GWAS uncovers putative loci in predisposition to elite sprint and power performance, health and disease

AU - Wang, Guan

AU - Fuku, Noriyuki

AU - Miyamoto-Mikami, Eri

AU - Tanaka, Masashi

AU - Miyachi, Motohiko

AU - Murakami, Haruka

AU - Mitchell, Braxton d.

AU - Morrison, Errol

AU - Ahmetov, Ildus

AU - Generozov, Edward

AU - Filipenko, Maxim l.

AU - Gilep, Andrei a.

AU - Gineviciene, Valentina

AU - Moran, Colin n.

AU - Venckunas, Tomas

AU - Cieszczyk, Pawel

AU - Derave, Wim

AU - Papadimitriou, Ioannis

AU - Garton, Fleur c.

AU - Padmanabhan, Sandosh

AU - Pitsiladis, Yannis p.

N1 - We would like to thank all participants of this project. We would also like to thank Dr Krista G. Austin for her contribution to the sample collection of the African-American athletes and controls, Dr. Olga N. Pyankova for her assistance in performing the genotyping replication of the European Cohort 1, Professor Kathryn North for providing resources and support for the replication study of the European Cohort 2, and Dr Yu-Ching Cheng for organizing and sharing the additional 350 African-American GWAS control genotype data. The GWAS genotyping work was funded by JSPS KAKENHI grant no. 15H03081 and 22H03486 to N.F. Genotyping replication in the Belorussian samples was funded by the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021\u20132030) grant no. 122030100168-2 to A.A.G. The additional 350 African American controls were drawn from the Genetics of Early Onset Stroke (GEOS) Study, with funding support from NIH U01 HG-004436 to B.D.M. The muscle biopsy study was supported by a grant from the Russian Science Foundation (grant no. 24-15-00413). Multi-phase, multi-ethnic GWAS uncovers putative loci in predisposition to elite sprint and power performance, health and disease / G. Wang, N. Fuku, E. Miyamoto-Mikami [et al.] // Biology of Sport. – 2025. – Vol. 42, No. 3. – P. 141-159. – DOI 10.5114/biolsport.2025.147015.

PY - 2025/1/1

Y1 - 2025/1/1

N2 - The genetic underpinnings of elite sprint and power performance remain largely elusive. This study aimed to identify genetic variants associated with this complex trait as well as to understand their functional implications in elite sprint and power performance. We conducted a multi-phase genome-wide association study (GWAS) in world-class sprint and power athletes of West African and East Asian ancestry and their geographically matched controls. We carried out genotype imputation, replications for the top GWAS signal rs10196189 in two European cohorts, and gene-based and tissue-specific functional network analyses. For the first time, we uncovered the G-allele of rs10196189 in the Polypeptide N Acetylgalactosaminyltransferase 13 (GALNT13) being significantly associated with elite sprint and power performance (P = 2.13E-09 across the three ancestral groups). Moreover, we found that GALNT13 expression level was positively associated with the relative area occupied by fast-twitch muscle fibers in the vastus lateralis muscle. In addition, significant and borderline associations were observed for BOP1, HSF1, STXBP2, GRM7, MPRIP, ZFYVE28, CERS4, and ADAMTS18 in cross-ancestry or ancestry-specific contexts, predominantly expressed in the nervous and hematopoietic systems. From the elite athlete cohorts, we further identified thirty-six previously uncharacterized genes linked to host defence, leukocyte migration, and cellular responses to interferon-gamma, and four genes – UQCRFS1, PTPN6, RALY and ZMYM4 – associated with aging, neurological conditions, and blood disorders. Taken together, these results provide new biological insights into the genetic basis of elite sprint and power performance and, importantly, offer valuable clues to the molecular mechanisms underlying elite athletic performance, health and disease.

AB - The genetic underpinnings of elite sprint and power performance remain largely elusive. This study aimed to identify genetic variants associated with this complex trait as well as to understand their functional implications in elite sprint and power performance. We conducted a multi-phase genome-wide association study (GWAS) in world-class sprint and power athletes of West African and East Asian ancestry and their geographically matched controls. We carried out genotype imputation, replications for the top GWAS signal rs10196189 in two European cohorts, and gene-based and tissue-specific functional network analyses. For the first time, we uncovered the G-allele of rs10196189 in the Polypeptide N Acetylgalactosaminyltransferase 13 (GALNT13) being significantly associated with elite sprint and power performance (P = 2.13E-09 across the three ancestral groups). Moreover, we found that GALNT13 expression level was positively associated with the relative area occupied by fast-twitch muscle fibers in the vastus lateralis muscle. In addition, significant and borderline associations were observed for BOP1, HSF1, STXBP2, GRM7, MPRIP, ZFYVE28, CERS4, and ADAMTS18 in cross-ancestry or ancestry-specific contexts, predominantly expressed in the nervous and hematopoietic systems. From the elite athlete cohorts, we further identified thirty-six previously uncharacterized genes linked to host defence, leukocyte migration, and cellular responses to interferon-gamma, and four genes – UQCRFS1, PTPN6, RALY and ZMYM4 – associated with aging, neurological conditions, and blood disorders. Taken together, these results provide new biological insights into the genetic basis of elite sprint and power performance and, importantly, offer valuable clues to the molecular mechanisms underlying elite athletic performance, health and disease.

KW - Polypeptide N-Acetylgalactosaminyltransferase 13

KW - GWAS

KW - Imputation

KW - Meta-analysis

KW - Genetic diversity

KW - Functional annotations

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105005964260&origin=inward&txGid=f23565ab0161f6b57580dbc258b8755d

UR - https://www.elibrary.ru/item.asp?id=82321611

U2 - 10.5114/biolsport.2025.147015

DO - 10.5114/biolsport.2025.147015

M3 - Article

VL - 42

SP - 141

EP - 159

JO - Biology of Sport

JF - Biology of Sport

SN - 0860-021X

IS - 3

ER -