{"doi":"10.3390/cells11233910","title":"Genome-Wide Association Study Identifies CDKN1A as a Novel Locus Associated with Muscle Fiber Composition","abstract":"Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.","journal":"Cells","year":2022,"id":247315,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9413,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":655557,"name":"Hirofumi Zempo","orcid":"0000-0003-2248-8580","position":1,"is_corresponding":false},{"id":884812,"name":"Eri Miyamoto‐Mikami","orcid":"0000-0002-4864-8581","position":2,"is_corresponding":false},{"id":291039,"name":"Hiroshi Kumagai","orcid":"0000-0002-0520-6214","position":3,"is_corresponding":false},{"id":884813,"name":"Andrey K. Larin","orcid":"0000-0002-9429-792X","position":4,"is_corresponding":false},{"id":884814,"name":"Rinat Sultanov","orcid":"0000-0003-3918-708X","position":5,"is_corresponding":false},{"id":885326,"name":"Konstantin Babalyan","orcid":null,"position":6,"is_corresponding":false},{"id":884815,"name":"Andrey V. Zhelankin","orcid":"0000-0002-3014-2005","position":7,"is_corresponding":false},{"id":884816,"name":"Takuro Tobina","orcid":"0000-0003-4789-2563","position":8,"is_corresponding":false},{"id":884817,"name":"Keisuke Shiose","orcid":"0000-0003-1089-9593","position":9,"is_corresponding":false},{"id":885327,"name":"Ryo Kakigi","orcid":null,"position":10,"is_corresponding":false},{"id":884818,"name":"Takamasa Tsuzuki","orcid":"0000-0002-0241-1183","position":11,"is_corresponding":false},{"id":884819,"name":"Noriko Ichinoseki‐Sekine","orcid":"0000-0002-0467-3312","position":12,"is_corresponding":false},{"id":884820,"name":"Hiroyuki Kobayashi","orcid":"0000-0001-8377-0091","position":13,"is_corresponding":false},{"id":884821,"name":"Hisashi Naıto","orcid":"0000-0002-0522-9512","position":14,"is_corresponding":false},{"id":884822,"name":"Jatin G. Burniston","orcid":"0000-0001-7303-9318","position":15,"is_corresponding":false},{"id":884823,"name":"Edward V. Generozov","orcid":"0000-0002-6314-4883","position":16,"is_corresponding":false},{"id":655558,"name":"Noriyuki Fuku","orcid":"0000-0001-7792-5835","position":17,"is_corresponding":false},{"id":884824,"name":"Ildus I. Ahmetov","orcid":"0000-0002-6335-4020","position":18,"is_corresponding":false},{"id":598400,"name":"Ekaterina A. Semenova","orcid":"0000-0003-1248-2855","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:23:53.369530Z","pmid":"36497168","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}