Article open access publication

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 10, 1, 2019

DOI:10.1038/s41467-018-08008-w, Dimensions: pub.1111593700, PMC: PMC6342931, PMID: 30670697,

Authors

Manning, Alisa (8) (9)
Aschard, Hugues (8) (11)
Wang, Zhe (12)
Smith, Albert V. (17) (29)
Chen, Xu (34)
Gao, Chuan (35)
He, Meian (38)
Kühnel, Brigitte (40) (41)
Rueedi, Rico (46) (47)
Boerwinkle, Eric (12) (54)
Ghanbari, Mohsen (15) (61)
He, Jiang (64)
Heng, Chew-Kiat (28) (66)
Hunt, Steven C. (67) (68)
Jonas, Jost B. (69) (70)
Koh, Woon-Puay (28) (71)
Kutalik, Zoltán (47) (72)
Liu, Jianjun (21) (66)
Meitinger, Thomas (74) (75)
Nalls, Mike A. (30) (79)
Peters, Annette (40) (84)
Polasek, Ozren (85) (86) (87)
Raitakari, Olli T. (88) (89)
Sofer, Tamar (7) (8)
Tang, Hua (95)
Tuomilehto, Jaakko (96) (97)
Yao, Jie (14)
Zhao, Wei (17)
Esko, Tõnu (31) (102)
Froguel, Philippe (33) (37)
Gasparini, Paolo (45) (55)
Gieger, Christian (41) (103)
Lakka, Timo A. (43) (65) (104)
Samani, Nilesh J. (44) (80)
van der Harst, Pim (32) (105)
Zheng, Wei (50)
Franks, Paul W. (8) (49) (98) (107)
Gudnason, Vilmundur (29) (108)
Ridker, Paul M. (7) (8)
Tai, E. Shyong (28) (66) (71)
van Dam, Rob M. (28) (66)
Psaty, Bruce M. (19) (93)

* Corresponding author

Affiliations

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  1. (1) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  2. (2) University of Copenhagen, grid.5254.6, KU
  3. (3) National Human Genome Research Institute, grid.280128.1
  4. (4) Leiden University Medical Center, grid.10419.3d
  5. (5) Washington University in St. Louis, grid.4367.6
  6. (6) University of Regensburg, grid.7727.5
  7. (7) Brigham and Women's Hospital, grid.62560.37
  8. (8) Harvard University, grid.38142.3c
  9. (9) Massachusetts General Hospital, grid.32224.35
  10. (10) Queen Mary University of London, grid.4868.2
  11. (11) Institut Pasteur, grid.428999.7
  12. (12) The University of Texas Health Science Center at Houston, grid.267308.8
  13. (13) University of North Carolina at Chapel Hill, grid.10698.36
  14. (14) Los Angeles Biomedical Research Institute, grid.279946.7
  15. (15) Erasmus University Medical Center, grid.5645.2
  16. (16) University of Alabama at Birmingham, grid.265892.2
  17. (17) University of Michigan, grid.214458.e
  18. (18) University of Mississippi Medical Center, grid.410721.1
  19. (19) University of Washington, grid.34477.33
  20. (20) University of Edinburgh, grid.4305.2
  21. (21) Genome Institute of Singapore, grid.418377.e
  22. (22) Boston University, grid.189504.1
  23. (23) University of Bristol, grid.5337.2
  24. (24) Federal University of Pelotas, grid.411221.5
  25. (25) University of Sao Paulo, grid.11899.38
  26. (26) Epidemiology and Biostatistics, University of Giorgia at Athens College of Public Health, 30602, Athens, GA, USA
  27. (27) Wake Forest Baptist Medical Center, grid.412860.9
  28. (28) National University Health System, grid.410759.e
  29. (29) Icelandic Heart Association, grid.420802.c
  30. (30) National Institute on Aging, grid.419475.a
  31. (31) University of Tartu, grid.10939.32
  32. (32) University Medical Center Groningen, grid.4494.d
  33. (33) Integrated Genomics and Metabolic Diseases Modeling, grid.463858.4
  34. (34) Karolinska Institute, grid.4714.6
  35. (35) Wake Forest University, grid.241167.7
  36. (36) University of Ioannina, grid.9594.1
  37. (37) Imperial College London, grid.7445.2
  38. (38) Huazhong University of Science and Technology, grid.33199.31
  39. (39) University of Cambridge, grid.5335.0
  40. (40) Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany
  41. (41) Helmholtz Zentrum München, grid.4567.0
  42. (42) Tampere University, grid.502801.e
  43. (43) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
  44. (44) University of Leicester, grid.9918.9
  45. (45) IRCCS Materno Infantile Burlo Garofolo, grid.418712.9
  46. (46) University of Lausanne, grid.9851.5
  47. (47) Swiss Institute of Bioinformatics, grid.419765.8
  48. (48) National Center For Global Health and Medicine, grid.45203.30
  49. (49) Skåne University Hospital, grid.411843.b
  50. (50) Vanderbilt University, grid.152326.1
  51. (51) Case Western Reserve University, grid.67105.35
  52. (52) Johns Hopkins University, grid.21107.35
  53. (53) University of Kentucky, grid.266539.d
  54. (54) Baylor College of Medicine, grid.39382.33
  55. (55) University of Trieste, grid.5133.4
  56. (56) Ninewells Hospital & Medical School, University of Dundee, DD1 9SY, Dundee, Scotland, UK
  57. (57) University of Kelaniya, grid.45202.31
  58. (58) Brown University, grid.40263.33
  59. (59) Hadassah Medical Center, grid.17788.31
  60. (60) The University of Texas Health Science Center, grid.468222.8
  61. (61) Mashhad University of Medical Sciences, grid.411583.a
  62. (62) Chinese Academy of Medical Sciences & Peking Union Medical College, grid.506261.6
  63. (63) National Institutes of Health, grid.94365.3d
  64. (64) Tulane University, grid.265219.b
  65. (65) University of Eastern Finland, grid.9668.1
  66. (66) National University of Singapore, grid.4280.e
  67. (67) Department of Genetic Medicine, Weill Cornell Medicine, 24144, Doha, Qatar
  68. (68) University of Utah, grid.223827.e
  69. (69) Heidelberg University, grid.7700.0
  70. (70) Capital Medical University, grid.24696.3f
  71. (71) Duke NUS Graduate Medical School, grid.428397.3
  72. (72) Institute of Social and Preventive Medicine, grid.482968.9
  73. (73) University of Virginia, grid.27755.32
  74. (74) Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany
  75. (75) Technical University of Munich, grid.6936.a
  76. (76) VU University Medical Center, grid.16872.3a
  77. (77) University of Mississippi, grid.251313.7
  78. (78) University of Aberdeen, grid.7107.1
  79. (79) Data Tecnica International, 20812, Glen Echo, MD, USA
  80. (80) Glenfield Hospital, grid.412925.9
  81. (81) University of Colorado Anschutz Medical Campus, grid.430503.1
  82. (82) University of Maryland, Baltimore, grid.411024.2
  83. (83) National Heart Lung and Blood Institute, grid.279885.9
  84. (84) German Centre for Cardiovascular Research, grid.452396.f
  85. (85) Gen-Info Ltd., 10000, Zagreb, Croatia
  86. (86) Psychiatric Hospital “Sveti Ivan”, 10000, Zagreb, Croatia
  87. (87) University of Split, grid.38603.3e
  88. (88) Turku University Hospital, grid.410552.7
  89. (89) University of Turku, grid.1374.1
  90. (90) University of California, San Francisco, grid.266102.1
  91. (91) University of Iowa, grid.214572.7
  92. (92) University of Minnesota, grid.17635.36
  93. (93) Kaiser Permanente Washington Health Research Institute, grid.488833.c
  94. (94) Ludwig Maximilian University of Munich, grid.5252.0
  95. (95) Stanford University, grid.168010.e
  96. (96) King Abdulaziz University, grid.412125.1
  97. (97) National Institute for Health and Welfare, grid.14758.3f
  98. (98) Umeå University, grid.12650.30
  99. (99) Jackson State University, grid.257990.0
  100. (100) Shanghai Jiao Tong University, grid.16821.3c
  101. (101) University of Pittsburgh, grid.21925.3d
  102. (102) Broad Institute, grid.66859.34
  103. (103) German Center for Diabetes Research, grid.452622.5
  104. (104) Kuopio University Hospital, grid.410705.7
  105. (105) Netherlands Heart Institute, grid.411737.7
  106. (106) University Hospital of Lausanne, grid.8515.9
  107. (107) Oxford Centre for Diabetes, Endocrinology and Metabolism, grid.470392.b
  108. (108) University of Iceland, grid.14013.37
  109. (109) Fred Hutchinson Cancer Research Center, grid.270240.3
  110. (110) University of Southern California, grid.42505.36
  111. (111) NHLBI Framingham Heart Study, 01702, Framingham, MA, USA

Description

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

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