Article open access publication

Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Nature Genetics, Springer Nature, ISSN 1061-4036

Volume 51, 4, 2019

DOI:10.1038/s41588-019-0378-y, Dimensions: pub.1113055529, PMC: PMC6467258, PMID: 30926973,

Authors

Cheng, Ching-Yu (12) (13) (14)
Sim, Xueling (12) (15)
Aschard, Hugues (6) (21)
Smith, Albert V. (27) (28)
Zhao, Wei (30)
Chai, Jin Fang (12) (15)
Chen, Xu (34)
Gao, Chuan (35)
Goel, Anuj (38) (39)
He, Meian (43)
Hung, Yi-Jen (45) (46)
Kühnel, Brigitte (49) (50)
Pietzner, Maik (55) (56)
Riaz, Muhammad (58) (59)
Sofer, Tamar (6) (7)
Wang, Tzung-Dau (66) (67)
Zhang, Weihua (37) (72)
Aung, Tin (12) (13) (14)
Boerwinkle, Eric (3) (74)
Duan, Qing (31)
Gao, He (37)
Ghanbari, Mohsen (16) (82)
Heng, Chew-Kiat (12) (15)
Joehanes, Roby (85) (86)
Jonas, Jost Bruno (87) (88)
Koh, Woon-Puay (12) (13) (15)
Lakka, Timo A. (48) (62) (93)
Li, Yize (2)
Liu, Jianjun (12) (24)
Liu, Kiang (95)
Loh, Marie (12) (37) (96) (97)
Louie, Tin (22)
Meitinger, Thomas (99) (100)
Morris, Andrew P. (38) (102)
Nalls, Mike A. (29) (104)
Nauck, Matthias (55) (56)
Peters, Annette (49) (106)
Polasek, Ozren (91) (107) (108)
Raitakari, Olli T. (109) (110)
Renström, Frida (65) (111)
Shi, Yuan (14)
Strauch, Konstantin (106) (115)
Tang, Hua (116)
Teo, Yik Ying (12) (15) (24)
Wang, Heming (6) (7)
Wang, Lan (8)
Yao, Jie (9)
Zhou, Jie (1)
Chambers, John C. (37) (72) (97) (120)
Esko, Tõnu (32) (121)
Farrall, Martin (38) (39)
Franks, Paul W. (6) (65) (111) (122)
Froguel, Philippe (33) (37)
Gasparini, Paolo (60) (81)
Gieger, Christian (49) (123)
Kooner, Jaspal S. (37) (72) (120)
Lee, I-Te (51) (124) (125)
Samani, Nilesh J. (58) (59)
Wang, Jun-Sing (51) (125)
Watkins, Hugh (38) (39)
Zeggini, Eleftheria (57) (126)
Zheng, Wei (69)
Psaty, Bruce M. (22) (127)
Ridker, Paul M. (6) (7)
van Dam, Rob M. (12) (15)
Tai, E. Shyong (12) (13) (15)
Wong, Tien Yin (12) (13) (14)

* Corresponding author

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  1. (1) National Human Genome Research Institute, grid.280128.1
  2. (2) Washington University in St. Louis, grid.4367.6
  3. (3) The University of Texas Health Science Center at Houston, grid.267308.8
  4. (4) University of Regensburg, grid.7727.5
  5. (5) Queen Mary University of London, grid.4868.2
  6. (6) Harvard University, grid.38142.3c
  7. (7) Brigham and Women's Hospital, grid.62560.37
  8. (8) Boston University, grid.189504.1
  9. (9) Los Angeles Biomedical Research Institute, grid.279946.7
  10. (10) Fred Hutchinson Cancer Research Center, grid.270240.3
  11. (11) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  12. (12) National University of Singapore, grid.4280.e
  13. (13) Duke NUS Graduate Medical School, grid.428397.3
  14. (14) Singapore National Eye Center, grid.419272.b
  15. (15) National University Health System, grid.410759.e
  16. (16) Erasmus University Medical Center, grid.5645.2
  17. (17) University of Edinburgh, grid.4305.2
  18. (18) University of Mississippi Medical Center, grid.410721.1
  19. (19) Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, USA
  20. (20) Leiden University Medical Center, grid.10419.3d
  21. (21) Institut Pasteur, grid.428999.7
  22. (22) University of Washington, grid.34477.33
  23. (23) Wake Forest Baptist Medical Center, grid.412860.9
  24. (24) Genome Institute of Singapore, grid.418377.e
  25. (25) Massachusetts General Hospital, grid.32224.35
  26. (26) Pennington Biomedical Research Center, grid.250514.7
  27. (27) Icelandic Heart Association, grid.420802.c
  28. (28) University of Iceland, grid.14013.37
  29. (29) National Institute on Aging, grid.419475.a
  30. (30) University of Michigan, grid.214458.e
  31. (31) University of North Carolina at Chapel Hill, grid.10698.36
  32. (32) University of Tartu, grid.10939.32
  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) Wellcome Centre for Human Genetics, grid.270683.8
  39. (39) University of Oxford, grid.4991.5
  40. (40) University Medical Center Groningen, grid.4494.d
  41. (41) University of Bristol, grid.5337.2
  42. (42) Federal University of Pelotas, grid.411221.5
  43. (43) Huazhong University of Science and Technology, grid.33199.31
  44. (44) University of Sao Paulo, grid.11899.38
  45. (45) National Defense Medical Center, grid.260565.2
  46. (46) Tri-Service General Hospital, grid.278244.f
  47. (47) University of Kelaniya, grid.45202.31
  48. (48) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
  49. (49) Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany
  50. (50) Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
  51. (51) Taichung Veterans General Hospital, grid.410764.0
  52. (52) University of Cambridge, grid.5335.0
  53. (53) Tampere University, grid.502801.e
  54. (54) RIKEN, grid.7597.c
  55. (55) University of Greifswald, grid.5603.0
  56. (56) German Centre for Cardiovascular Research, grid.452396.f
  57. (57) Wellcome Sanger Institute, grid.10306.34
  58. (58) Glenfield Hospital, grid.412925.9
  59. (59) University of Leicester, grid.9918.9
  60. (60) IRCCS Materno Infantile Burlo Garofolo, grid.418712.9
  61. (61) Columbia University Medical Center, grid.239585.0
  62. (62) University of Eastern Finland, grid.9668.1
  63. (63) National Center For Global Health and Medicine, grid.45203.30
  64. (64) Loyola University Chicago, grid.164971.c
  65. (65) Skåne University Hospital, grid.411843.b
  66. (66) National Taiwan University, grid.19188.39
  67. (67) National Taiwan University Hospital, grid.412094.a
  68. (68) Case Western Reserve University, grid.67105.35
  69. (69) Vanderbilt University, grid.152326.1
  70. (70) Shanghai Jiao Tong University, grid.16821.3c
  71. (71) Johns Hopkins University, grid.21107.35
  72. (72) Ealing Hospital, grid.415918.0
  73. (73) Houston Methodist, grid.63368.38
  74. (74) Baylor College of Medicine, grid.39382.33
  75. (75) Medical College of Wisconsin, grid.30760.32
  76. (76) University of Southern Denmark, grid.10825.3e, SDU
  77. (77) University of Dundee, grid.8241.f
  78. (78) Brown University, grid.40263.33
  79. (79) University of the West Indies, grid.12916.3d
  80. (80) Braun School of Public Health, Hebrew University–Hadassah Medical Center, Jerusalem, Israel
  81. (81) University of Trieste, grid.5133.4
  82. (82) Mashhad University of Medical Sciences, grid.411583.a
  83. (83) National Institutes of Health, grid.94365.3d
  84. (84) University of Tokyo, grid.26999.3d
  85. (85) Hebrew SeniorLife, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
  86. (86) National Heart Lung and Blood Institute, grid.279885.9
  87. (87) Heidelberg University, grid.7700.0
  88. (88) Capital Medical University, grid.24696.3f
  89. (89) Osaka University, grid.136593.b
  90. (90) University of Copenhagen, grid.5254.6, KU
  91. (91) University of Split, grid.38603.3e
  92. (92) RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  93. (93) Kuopio University Hospital, grid.410705.7
  94. (94) University of Alabama at Birmingham, grid.265892.2
  95. (95) Northwestern University, grid.16753.36
  96. (96) Agency for Science, Technology and Research, grid.185448.4
  97. (97) Nanyang Technological University, grid.59025.3b
  98. (98) University of Virginia, grid.27755.32
  99. (99) Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  100. (100) Technical University of Munich, grid.6936.a
  101. (101) VU Amsterdam, grid.12380.38
  102. (102) University of Liverpool, grid.10025.36
  103. (103) University of Aberdeen, grid.7107.1
  104. (104) Data Tecnica International, Glen Echo, MD, USA
  105. (105) University of Maryland, Baltimore, grid.411024.2
  106. (106) Ludwig Maximilian University of Munich, grid.5252.0
  107. (107) Gen-info, Ltd, Zagreb, Croatia
  108. (108) Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia
  109. (109) Turku University Hospital, grid.410552.7
  110. (110) University of Turku, grid.1374.1
  111. (111) Umeå University, grid.12650.30
  112. (112) University of Iowa, grid.214572.7
  113. (113) University of Minnesota, grid.17635.36
  114. (114) Kaiser Permanente, grid.280062.e
  115. (115) Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  116. (116) Stanford University, grid.168010.e
  117. (117) Mayo Clinic, grid.66875.3a
  118. (118) Jackson State University, grid.257990.0
  119. (119) University of Pittsburgh, grid.21925.3d
  120. (120) Imperial College Healthcare NHS Trust, grid.417895.6
  121. (121) Broad Institute, grid.66859.34
  122. (122) Oxford Centre for Diabetes, Endocrinology and Metabolism, grid.470392.b
  123. (123) German Center for Diabetes Research, grid.452622.5
  124. (124) Chung Shan Medical University, grid.411641.7
  125. (125) National Yang Ming University, grid.260770.4
  126. (126) Institute of Translational Genomics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  127. (127) Kaiser Permanente Washington Health Research Institute, grid.488833.c
  128. (128) Tulane University, grid.265219.b
  129. (129) University of Southern California, grid.42505.36

Description

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

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Times Cited: 35

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Green, Accepted