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GWAS OF HISTOLOGICAL PHENOTYPES PROVIDES INSIGHTS INTO THE GENETIC ARCHITECTURE OF HUMAN SKELETAL MUSCLE
Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. LUDC, Lunds Universitet. (Swedish Winter Sports Research Centre)
Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences. (Swedish Winter Sports Research Centre)ORCID iD: 0000-0002-3814-6246
2015 (English)In: ABSTRACT BOOK for the SGGD 2015, 2015Conference paper, Abstract (Refereed)
Abstract [en]

Introduction

Athlete performance depends to some extent on skeletal muscle fiber-type composition, i.e. athletes practicing endurance sports usually have a higher proportion of slow-twitch type I fibers, while fast-twitch type II fibers are more common for athletes in explosive sports. Insulin sensitivity has also been correlated with proportion of type I fibers, i.e. insulin resistant individuals having reduced muscle oxidative capacity with less oxidative type I and more glycolytic type IIx fibers.

Aims

Here we aimed to identify genetic variation and corresponding biological mechanisms affecting human skeletal muscle histology.

Methods

We performed a genome-wide association meta-analysis in Swedish males from 3 independent cohorts (n=656) with skeletal muscle histological phenotypes, e.g. capillary density, fibre-type distribution and area (measured by ATPas staining). Skeletal muscle microarray expression data (n=77) were used for an eQTL analysis of associated markers. Follow-up of capillary density was done in Swedish elite cross-country skiers (n=15).

Results

We identified 11 genome-wide significant (p<5x10-8) independent loci (STEAP, NYAP2, ADRA1B, TNFSF11, FAM155A, SLC22A10, FASLG, RBFOX1, FOXJ2, KCNMA1, RAB3GAP2) associated with 6 skeletal muscle phenotypes. eQTL-genes corresponding to the top associated variants were enriched in metabolic pathways. Using a population differentiation neutrality test we show that some of the fibre-type nominally associated loci (p<1x10-6) fall within regions of positive selection (i.e. FHIT, CRISP and ANXA1). The G-allele of rs115660502 (MAF=0.048) was significantly associated (p=2x10-8) with increased capillary density and also decreased expression of the nearby gene RAB3GAP2 (FDR=0.007). The G-allele also had a significantly higher frequency (MAF=0.122, p=0.029) in the cohort of Swedish elite skiers.

Conclusion

Our results add to our understanding of skeletal muscle architecture and indicate that there is a genetic component to it and that this might contribute to increased endurance performance in sport athletes.

Place, publisher, year, edition, pages
2015.
National Category
Physiology Biological Sciences
Identifiers
URN: urn:nbn:se:miun:diva-26815OAI: oai:DiVA.org:miun-26815DiVA: diva2:890828
Conference
SGGD 2015, Krakow
Available from: 2016-01-04 Created: 2016-01-04 Last updated: 2016-01-05Bibliographically approved

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