Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

@article{Zillikens2017LargeMO,
  title={Large meta-analysis of genome-wide association studies identifies five loci for lean body mass},
  author={M. Zillikens and S. Demissie and Y. Hsu and L. Yerges-Armstrong and Wen-Chi Chou and L. Stolk and G. Livshits and L. Broer and T. Johnson and Daniel L. Koller and Z. Kutalik and J. Luan and I. Malkin and J. Ried and Albert Vernon Smith and G. Thorleifsson and L. Vandenput and Jing Hua Zhao and Weihua Zhang and A. Aghdassi and K. Akesson and N. Amin and L. Baier and I. Barroso and D. Bennett and L. Bertram and Rainer Biffar and M. Bochud and M. Boehnke and I. Borecki and A. Buchman and L. Byberg and H. Campbell and Natalia Campos Obanda and J. Cauley and P. Cawthon and H. Cederberg and Zhao Chen and N. Cho and Hyung Jin Choi and M. Claussnitzer and F. Collins and S. Cummings and P. D. De Jager and I. Demuth and R. Dhonukshe-Rutten and L. Diatchenko and G. Eiriksdottir and A. Enneman and M. Erdos and J. Eriksson and K. Estrada and Daniel S. Evans and M. Feitosa and Mao Fu and M. Garcia and C. Gieger and T. Girke and N. Glazer and H. Grallert and Jagvir Grewal and B. Han and R. Hanson and C. Hayward and A. Hofman and E. Hoffman and G. Homuth and W. Hsueh and Monica Jeanne Hubal and A. Hubbard and K. Huffman and L. Husted and T. Illig and E. Ingelsson and T. Ittermann and J. Jansson and J. Jordan and A. Jula and M. Karlsson and K. Khaw and T. Kilpel{\"a}inen and N. Klopp and J. Kloth and H. Koistinen and W. Kraus and S. Kritchevsky and T. Kuulasmaa and J. Kuusisto and M. Laakso and J. Lahti and T. Lang and B. Langdahl and L. Launer and Jong-Young Lee and M. Lerch and Joshua R. Lewis and L. Lind and C. Lindgren and Yongmei Liu and Tian Liu and Youfang Liu and {\"O}. Ljunggren and M. Lorentzon and R. Luben and W. Maixner and F. McGuigan and C. Medina-Gomez and T. Meitinger and H. Melhus and D. Mellstr{\"o}m and S. Melov and K. Micha{\"e}lsson and B. Mitchell and A. Morris and L. Mosekilde and A. Newman and C. Nielson and J. O'Connell and B. Oostra and E. Orwoll and A. Palotie and Stephen C. J. Parker and M. Peacock and M. Perola and A. Peters and O. Pola{\vs}ek and R. Prince and K. R{\"a}ikk{\"o}nen and S. Ralston and S. Ripatti and J. Robbins and J. Rotter and I. Rudan and V. Salomaa and S. Satterfield and E. Schadt and S. Schipf and L. Scott and J. Sehmi and Jian Shen and Chan Soo Shin and G. Sigurdsson and Shad B Smith and N. Soranzo and A. Stan{\vc}{\'a}kov{\'a} and E. Steinhagen-Thiessen and E. Streeten and U. Styrkarsdottir and K. Swart and Sian-Tsung Tan and M. Tarnopolsky and Patricia Thompson and C. Thomson and U. Thorsteinsdottir and E. Tikkanen and G. Tranah and J. Tuomilehto and N. V. van Schoor and Arjun Verma and P. Vollenweider and H. V{\"o}lzke and J. Wactawski-Wende and M. Walker and M. Weedon and R. Welch and H. Wichmann and E. Wid{\'e}n and F. Williams and James F. Wilson and N. Wright and Weijia Xie and Lei Yu and Y. Zhou and J. Chambers and A. D{\"o}ring and C. V. van Duijn and M. Econs and V. Gudnason and J. Kooner and B. Psaty and T. Spector and K. Stef{\'a}nsson and F. Rivadeneira and A. Uitterlinden and N. Wareham and V. Ossowski and D. Waterworth and R. Loos and D. Karasik and T. Harris and C. Ohlsson and D. Kiel},
  journal={Nature Communications},
  year={2017},
  volume={8}
}
Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide… Expand
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References

SHOWING 1-10 OF 183 REFERENCES
Association of FTO gene variants with body composition in UK twins
TLDR
The results suggest that the association between FTO variants and body composition phenotypes is present across a wide range of ages, and that FTO appears primarily to affect the amount of body soft tissue, influencing both fat and lean mass. Expand
Linkage of genes to total lean body mass in normal women.
TLDR
This first genomic search for genes associated with the lean component of body mass suggests significant linkage to quantitative trait loci on chromosomes 12 and 14, which is highly heritable, independent of other body measures. Expand
Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study
TLDR
The importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass is suggested, suggesting the gene’s dual role in both bone development and muscle growth. Expand
Genome-wide search for genes related to the fat-free body mass in the Québec family study.
TLDR
This study represents the first genome-wide search for genes that may be involved in the regulation of the lean component of body mass in humans. Expand
Genome-wide association and replication studies identified TRHR as an important gene for lean body mass.
TLDR
Results of this study support the TRHR gene as an important gene for LBM variation, together with the functional relevance of TRHR in muscle metabolism, by using Affymetrix 500K single-nucleotide polymorphism (SNP) arrays. Expand
Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass
TLDR
The results suggest that the gremlin1 gene is a potentially important gene for LBM variation and the utility and efficacy of CNV as genetic markers in association studies are shown. Expand
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzedExpand
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
TLDR
This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI and the sex-specificity of Genetic Investigation of Anthropometric Traits (GIANT) Consortium, and it is confirmed that this effect is related to weight change with age or the sexually dimorphism of body shape. Expand
Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution
TLDR
By focusing on anthropometric measures of central obesity and fat distribution, a meta-analysis of 16 genome-wide association studies informative for adult waist circumference and waist–hip ratio identified three loci implicated in the regulation of human adiposity. Expand
A Meta-Analysis Identifies New Loci Associated with Body Mass index in Individuals of African Ancestry
TLDR
A meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals ofAfrican ancestry provides strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations. Expand
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