scholarly journals Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle

2019 ◽  
Vol 116 (22) ◽  
pp. 10883-10888 ◽  
Author(s):  
D. Leland Taylor ◽  
Anne U. Jackson ◽  
Narisu Narisu ◽  
Gibran Hemani ◽  
Michael R. Erdos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Muscle Fiber ◽  
Quantitative Trait ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Genetic Associations

We integrate comeasured gene expression and DNA methylation (DNAme) in 265 human skeletal muscle biopsies from the FUSION study with >7 million genetic variants and eight physiological traits: height, waist, weight, waist–hip ratio, body mass index, fasting serum insulin, fasting plasma glucose, and type 2 diabetes. We find hundreds of genes and DNAme sites associated with fasting insulin, waist, and body mass index, as well as thousands of DNAme sites associated with gene expression (eQTM). We find that controlling for heterogeneity in tissue/muscle fiber type reduces the number of physiological trait associations, and that long-range eQTMs (>1 Mb) are reduced when controlling for tissue/muscle fiber type or latent factors. We map genetic regulators (quantitative trait loci; QTLs) of expression (eQTLs) and DNAme (mQTLs). Using Mendelian randomization (MR) and mediation techniques, we leverage these genetic maps to predict 213 causal relationships between expression and DNAme, approximately two-thirds of which predict methylation to causally influence expression. We use MR to integrate FUSION mQTLs, FUSION eQTLs, and GTEx eQTLs for 48 tissues with genetic associations for 534 diseases and quantitative traits. We identify hundreds of genes and thousands of DNAme sites that may drive the reported disease/quantitative trait genetic associations. We identify 300 gene expression MR associations that are present in both FUSION and GTEx skeletal muscle and that show stronger evidence of MR association in skeletal muscle than other tissues, which may partially reflect differences in power across tissues. As one example, we find that increased RXRA muscle expression may decrease lean tissue mass.

Human Skeletal Muscle Fiber Types: Delineation, Development, and Distribution

1997 ◽  
Vol 22 (4) ◽  
pp. 307-327 ◽  
Author(s):  
Robert S. Staron
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Skeletal Muscle Fiber ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Key Words Aging ◽  
Fiber Number ◽  
Human Limb

This brief review attempts to summarize a number of studies on the delineation, development, and distribution of human skeletal muscle fiber types. A total of seven fiber types can be identified in human limb and trunk musculature based on the pH stability/ability of myofibrillar adenosine triphosphatase (mATPase). For most human muscles, mATPase-based fiber types correlate with the myosin heavy chain (MHC) content. Thus, each histochemically identified fiber has a specific MHC profile. Although this categorization is useful, it must be realized that muscle fibers are highly adaptable and that innumerable fiber type transients exist. Also, some muscles contain specific MHC isoforms and/or combinations that do not permit routine mATPase-based fiber typing. Although the major populations of fast and slow are, for the most part, established shortly after birth, subtle alterations take place throughout life. These changes appear to relate to alterations in activity and/or hormonal levels, and perhaps later in life, total fiber number. Because large variations in fiber type distribution can be found within a muscle and between individuals, interpretation of data gathered from human muscle is often difficult. Key words: aging, myosin heavy chains, myogenesis, myofibrillar adenosine triphosphate

Gene Polymorphisms and Fiber-Type Composition of Human Skeletal Muscle

2012 ◽  
Vol 22 (4) ◽  
pp. 292-303 ◽  
Author(s):  
Ildus I. Ahmetov ◽  
Olga L. Vinogradova ◽  
Alun G. Williams
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Fiber Types ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Type I Fibers

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

scholarly journals Human skeletal muscle fiber type adaptability to various workloads.

1984 ◽  
Vol 32 (2) ◽  
pp. 146-152 ◽  
Author(s):  
R S Staron ◽  
R S Hikida ◽  
F C Hagerman ◽  
G A Dudley ◽  
T F Murray
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Skeletal Muscle Fiber ◽  
Muscle Fiber Type

Muscle Fiber Type Changes in Human Skeletal Muscle After Injuries and Immobilization

Orthopedics ◽  
1986 ◽  
Vol 9 (2) ◽  
pp. 181-185
Author(s):  
Tom Häggmark ◽  
Ejnar Eriksson ◽  
Eva Jansson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Muscle Fiber Type

scholarly journals Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

PLoS Medicine ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. e1002215 ◽  
Author(s):  
Michael M. Mendelson ◽  
Riccardo E. Marioni ◽  
Roby Joehanes ◽  
Chunyu Liu ◽  
Åsa K. Hedman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Blood Cells ◽  
Mendelian Randomization ◽  
Cardiometabolic Disease

scholarly journals Expression of fos andjun genes in human skeletal muscle after exercise

1998 ◽  
Vol 274 (1) ◽  
pp. C129-C137 ◽  
Author(s):  
A. Puntschart ◽  
E. Wey ◽  
K. Jostarndt ◽  
M. Vogt ◽  
M. Wittwer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Muscle Fiber ◽  
Protein Level ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Family Members ◽  
Gene Families ◽  
Differential Regulation ◽  
Genetic Events

It is believed that the induction of the fos and jun gene family of transcription factors might be at the origin of genetic events leading to the differential regulation of muscle-specific genes. We have investigated the effect of a 30-min running bout in untrained subjects on the expression of the mRNAs of all members of the fos and jun gene families, including c- fos, fosB, fosBdel, fra-1, and fra-2 as well as c- jun, junB, and junD. While the fos family members were transiently upregulated 10- to 20-fold (an exception being fra-2), the induction of the jun family members was up to 3-fold only. The induction of c- fos could also be demonstrated at the protein level. Both c- fos and c- jun mRNAs were coinduced in muscle fiber nuclei. The induction was not restricted to a particular fiber type, as expected from established muscle fiber recruitment schemes, but followed a “patchy” pattern confined to certain regions of the muscle. The signals leading to the expression of these immediate early genes are therefore unclear.

scholarly journals Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle

Diabetologia ◽  
2008 ◽  
Vol 51 (7) ◽  
pp. 1159-1168 ◽  
Author(s):  
T. Rönn ◽  
P. Poulsen ◽  
O. Hansson ◽  
J. Holmkvist ◽  
P. Almgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Human Skeletal Muscle
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