Article open access publication

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

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 8, 1, 2017

DOI:10.1038/s41467-017-00031-7, Dimensions: pub.1090696177, PMC: PMC5517526, PMID: 28724990,

Authors

Chou, Wen-Chi (4) (6)
Stolk, Lisette (1) (2)
Johnson, Toby (9) (10) (11)
Kutalik, Zoltán (9) (10) (11)
Smith, Albert V. (15) (16)
Zhang, Weihua (19) (20)
Åkesson, Kristina (22) (23)
Barroso, Inês (25) (26) (27)
Bertram, Lars (19) (29)
Cederberg, Henna (36) (37)
Chen, Zhao (38)
Jin Choi, Hyung (40) (41)
Claussnitzer, Melina (4) (6) (42) (43) (44)
De Jager, Philip L (4) (6) (46)
Demuth, Ilja (47) (48)
Diatchenko, Luda (49) (50)
Eriksson, Johan G. (51) (52) (53) (54) (55)
Fu, Mao (5)
Gieger, Christian (14) (57)
Grallert, Harald (14) (57) (58) (59) (60)
Grewal, Jagvir (19) (20)
Hofman, Albert (1) (2)
Hubal, Monica J. (63) (64)
Illig, Thomas (57) (68)
Ingelsson, Erik (32) (69)
Kilpeläinen, Tuomas O. (13) (70) (71)
Klopp, Norman (57) (68)
Koistinen, Heikki A (54) (72) (73) (74)
Kuulasmaa, Teemu (36) (37)
Kuusisto, Johanna (36) (37)
Laakso, Markku (36) (37)
Lewis, Joshua R (77) (78)
Lind, Lars (32)
Liu, Tian (80) (81)
Meitinger, Thomas (43) (82)
Melov, Simon (83) (84)
Morris, Andrew P. (79) (86)
Oostra, Ben A (2) (88)
Perola, Markus (54) (55) (89)
Peters, Annette (14) (57)
Prince, Richard L (78) (91)
Ripatti, Samuli (27) (55)
Sehmi, Joban (19) (20)
Shen, Jian (87)
Sigurdsson, Gunnar (15) (96)
Tan, Sian-Tsung (19) (20)
Tikkanen, Emmi (54) (55) (92)
Tuomilehto, Jaakko (53) (101) (102) (103)
Walker, Mark (106)
Wichmann, H.-Erich (14) (43) (108)
Xie, Weijia (107)
Yu, Lei (28)
Chambers, John C. (19) (20) (110) (111)
Döring, Angela (14) (112)
Kooner, Jaspal S. (19) (20) (111)
Psaty, Bruce M (113) (114)
Stefansson, Kari (15) (17)
Loos, Ruth J F (13) (71)
Karasik, David (4) (116)
Kiel, Douglas P * (4) (44)

* Corresponding author

Affiliations

Organisations

  1. (1) Wageningen University & Research, grid.4818.5
  2. (2) Erasmus University Medical Center, grid.5645.2
  3. (3) Boston University, grid.189504.1
  4. (4) Harvard University, grid.38142.3c
  5. (5) University of Maryland, Baltimore, grid.411024.2
  6. (6) Broad Institute, grid.66859.34
  7. (7) Tel Aviv University, grid.12136.37
  8. (8) King's College London, grid.13097.3c
  9. (9) Swiss Institute of Bioinformatics, grid.419765.8
  10. (10) University of Lausanne, grid.9851.5
  11. (11) Centre Hospitalier Universitaire (CHUV), University Institute for Social and Preventive Medicine, 1010, Lausanne, Switzerland
  12. (12) Indiana University – Purdue University Indianapolis, grid.257413.6
  13. (13) University of Cambridge, grid.5335.0
  14. (14) Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, 85764, Neuherberg, Germany
  15. (15) University of Iceland, grid.14013.37
  16. (16) Icelandic Heart Association, grid.420802.c
  17. (17) deCODE Genetics (Iceland), grid.421812.c
  18. (18) University of Gothenburg, grid.8761.8
  19. (19) Imperial College London, grid.7445.2
  20. (20) Ealing Hospital NHS Trust, grid.412922.e
  21. (21) University of Greifswald, grid.5603.0
  22. (22) Skåne University Hospital, grid.411843.b
  23. (23) Lund University, grid.4514.4
  24. (24) National Institute of Diabetes and Digestive and Kidney Diseases, grid.419635.c
  25. (25) Institute of Metabolic Science, grid.470900.a
  26. (26) NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke’s Hospital, CB2 OQQ, Cambridge, UK
  27. (27) Wellcome Sanger Institute, grid.10306.34
  28. (28) Rush University Medical Center, grid.240684.c
  29. (29) University of Lübeck, grid.4562.5
  30. (30) University of Michigan, grid.214458.e
  31. (31) Washington University in St. Louis, grid.4367.6
  32. (32) Uppsala University, grid.8993.b
  33. (33) University of Edinburgh, grid.4305.2
  34. (34) University of Pittsburgh, grid.21925.3d
  35. (35) California Pacific Medical Center, grid.17866.3e
  36. (36) Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210, Kuopio, Finland
  37. (37) Kuopio University Hospital, grid.410705.7
  38. (38) University of Arizona, grid.134563.6
  39. (39) Ajou University, grid.251916.8
  40. (40) Chungbuk National University Hospital, grid.411725.4
  41. (41) Seoul National University, grid.31501.36
  42. (42) Massachusetts Institute of Technology, grid.116068.8
  43. (43) Technical University of Munich, grid.6936.a
  44. (44) Beth Israel Deaconess Medical Center, grid.239395.7
  45. (45) National Human Genome Research Institute, grid.280128.1
  46. (46) Brigham and Women's Hospital, grid.62560.37
  47. (47) Charité, grid.6363.0
  48. (48) Lipid Clinic at the Interdisciplinary Metabolism Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353, Berlin, Germany
  49. (49) McGill University, grid.14709.3b
  50. (50) University of North Carolina at Chapel Hill, grid.10698.36
  51. (51) Folkhälsans Forskningscentrum, grid.428673.c
  52. (52) Helsinki University Central Hospital, grid.15485.3d
  53. (53) Vaasa Central Hospital, grid.417201.1
  54. (54) National Institute for Health and Welfare, grid.14758.3f
  55. (55) University of Helsinki, grid.7737.4
  56. (56) National Institutes of Health, grid.94365.3d
  57. (57) Helmholtz Zentrum München, grid.4567.0
  58. (58) University of California, Riverside, grid.266097.c
  59. (59) CCG Nutrigenomics and Type 2 Diabetes. Helmholtz Zentrum München, 85764, Neuherberg, Germany
  60. (60) German Center for Diabetes Research, grid.452622.5
  61. (61) Korea National Institute of Health, grid.415482.e
  62. (62) Binghamton University, grid.264260.4
  63. (63) Children’s National Health System, grid.239560.b
  64. (64) George Washington University, grid.253615.6
  65. (65) University of California, Berkeley, grid.47840.3f
  66. (66) Duke University, grid.26009.3d
  67. (67) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  68. (68) Hannover Medical School, grid.10423.34
  69. (69) Stanford University, grid.168010.e
  70. (70) University of Copenhagen, grid.5254.6, KU
  71. (71) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  72. (72) Department of Medicine, University of Helsinki and Helsinki University Central Hospital, 00029, Helsinki, Finland
  73. (73) Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Central Hospital, 00029, Helsinki, Finland
  74. (74) Minerva Foundation, grid.452540.2
  75. (75) Wake Forest University, grid.241167.7
  76. (76) University of California, San Francisco, grid.266102.1
  77. (77) University of Sydney, grid.1013.3
  78. (78) University of Western Australia, grid.1012.2
  79. (79) Wellcome Centre for Human Genetics, grid.270683.8
  80. (80) Max Planck Institute for Human Development, grid.419526.d
  81. (81) Max Planck Institute for Molecular Genetics, grid.419538.2
  82. (82) Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764, Neuherberg, Germany
  83. (83) Buck Institute for Research on Aging, grid.272799.0
  84. (84) University of Southern California, grid.42505.36
  85. (85) Baltimore VA Medical Center, grid.280711.d
  86. (86) University of Liverpool, grid.10025.36
  87. (87) Oregon Health & Science University, grid.5288.7
  88. (88) Centre for Medical Systems Biology, grid.450025.6
  89. (89) University of Tartu, grid.10939.32
  90. (90) University of Split, grid.38603.3e
  91. (91) Department of Endocrinology and Diabetes, Sir Charles Gardiner Hospital, 6009, Perth, Australia
  92. (92) Western General Hospital, grid.417068.c
  93. (93) University of California, Davis, grid.27860.3b
  94. (94) Harbor–UCLA Medical Center, grid.239844.0
  95. (95) University of Tennessee Health Science Center, grid.267301.1
  96. (96) National University Hospital of Iceland, grid.410540.4
  97. (97) Duke University Hospital, grid.189509.c
  98. (98) EMGO Institute for Health and Care Research, grid.466632.3
  99. (99) McMaster University Medical Centre, grid.411657.0
  100. (100) Stony Brook University, grid.36425.36
  101. (101) Danube University Krems, grid.15462.34
  102. (102) Dasman Diabetes Institute, grid.452356.3
  103. (103) King Abdulaziz University, grid.412125.1
  104. (104) University Hospital of Lausanne, grid.8515.9
  105. (105) University at Buffalo, State University of New York, grid.273335.3
  106. (106) Newcastle University, grid.1006.7
  107. (107) University of Exeter, grid.8391.3
  108. (108) Ludwig Maximilian University of Munich, grid.5252.0
  109. (109) University of Alabama at Birmingham, grid.265892.2
  110. (110) National Institute for Health Research, grid.451056.3
  111. (111) Imperial College Healthcare NHS Trust, grid.417895.6
  112. (112) Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764, Neuherberg, Germany
  113. (113) PricewaterhouseCoopers (United States), grid.422767.2
  114. (114) University of Washington, grid.34477.33
  115. (115) GlaxoSmithKline (United States), grid.418019.5
  116. (116) Bar-Ilan University, grid.22098.31

Description

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 (p < 5 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Aarhus University

Danish Open Access Indicator

2017: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2017: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 55

Field Citation Ratio (FCR): 11.56

Relative Citation ratio (RCR): 3.87

Open Access Info

Pure Gold