Evidence map›Paper›PMID 27144936›Full record

ArticleThe Journal of clinical endocrinology and metabolism2016

Contribution of Heritability and Epigenetic Factors to Skeletal Muscle Mass Variation in United Kingdom Twins.

Gregory Livshits, Fei Gao, Ida Malkin, Maria Needhamsen, Yudong Xia, Wei Yuan, Christopher G Bell, Kirsten Ward, Yuan Liu, Jun Wang and 2 more

Abstract readTwin Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. NADMolecular and cellular biochemistry · 2022
    Review
  14. Observational
  15. Article
  16. Article
  17. TNF Receptor-Associated Factor 6 Mediates TNFα-Induced Skeletal Muscle Atrophy in Mice During Aging.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Gregory LivshitsDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Fei GaoDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Ida MalkinDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Maria NeedhamsenDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Yudong XiaDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Wei YuanDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Christopher G BellDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Kirsten WardDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Yuan LiuDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Jun WangDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Jordana T BellDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.
Tim D SpectorDepartment of Twin Research and Genetic Epidemiology (G.L., M.N., W.Y., C.G.B., K.W., J.T.B., T.D.S.), King's College London, London SE1 7EH, United Kingdom; Human Population Biology Research Unit (G.L., I.M.), Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Beijing Genomics Institute-Shenzhen (F.G., Y.X., Y.L., J.W.), Shenzhen 518083, China; King Abdulaziz University (J.W.), Jeddah 22254, Saudi Arabia; and Department of Biology (J.W.) and The Novo Nordisk Foundation Center for Basic Metabolic Research (J.W.), University of Copenhagen, Copenhagen DK-2200, Denmark.

Funding

Wellcome Trust
6 · The paper itself

Abstract

contextSkeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia.

objectiveOur major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM.

designThis was a mixed cross-sectional and longitudinal study.

settingCommunity-based study.

participantsA total of 1550 middle-aged United Kingdom twins (monozygotic [MZ] and dizygotic [DZ]), 297 of which were repeatedly measured participated in the study.

main outcome measureAppendicular lean mass assessed using dual-energy X-ray absorptiometry technology, and methylated DNA immunoprecipitation sequencing DNA methylation profiling genome-wide were obtained from each individual.

resultsHeritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis, was h(2) = 0.809 ± 0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723 029 genomic sites, with positive correlations between repeated measurements (Rrepeated = 0.114-0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively, and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36 081 nominally significant results, of which the top-ranked 134 signals (P < .01 and Rrepeated > 0.40) were subjected to replication in the sample of 1196 individuals. Seven SMM methylation association signals replicated at a false discovery rate less than 0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, and ZFP64, which have previously been highlighted in muscle-related studies. Adjusting for age, smoking, and blood cell heterogeneity did not alter significance of these associations.

conclusionThis epigenome-wide study, testing longitudinally stable methylation sites, discovered and replicated a number of associations between DNA methylation at CpG loci and SMM. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation.

Indexed as

DNA MethylationAbsorptiometry, PhotonBody CompositionCross-Sectional StudiesDNA-Binding ProteinsDyneinsGenetic Association StudiesHumansLongitudinal StudiesMuscle, SkeletalRegistriesTranscription FactorsTwins, DizygoticTwins, MonozygoticUnited KingdomCAND1 protein, humanDNA-Binding ProteinsDNAH12 protein, humanDyneinsTranscription FactorsZFP64 protein, human

Identifiers

PMID27144936
PMCPMC4891794

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.