Article open access publication

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 8, 1, 2017

DOI:10.1038/ncomms14977, Dimensions: pub.1085060523, PMC: PMC5414044, PMID: 28443625,

Authors

Barata, Llilda (3) (4)
Hadley, David (6) (7)
Ngwa, Julius S. (5) (8)
Chu, Audrey Y (11) (12)
Kutalik, Zoltán (15) (16) (17)
Renström, Frida (19) (20)
Qi, Qibin (21)
Ahmad, Shafqat (12) (20) (22)
Corre, Tanguy (15) (16) (17)
Direk, Nese (24) (30)
Gorski, Mathias (2) (33)
Horikoshi, Momoko (18) (34)
Huang, Tao (22) (35)
Kumari, Meena (41) (42)
Lim, Unhee (43)
Mangino, Massimo (46) (47)
Müller-Nurasyid, Martina (50) (51) (52)
Wu, Ying (71)
Zhang, Weihua (72) (73)
Afaq, Saima (72) (73)
Afzal, Uzma (72) (73)
Beilby, John (27) (76) (77)
Bergmann, Sven (16) (17)
Chambers, John C. (72) (73) (84)
De Geus, Eco J C N (70) (85)
Esko, Tõnu (32) (66) (67)
Ford, Ian (87)
Gertow, Karl (58) (59)
Gong, Jian (74)
Grallert, Harald (52) (90)
Hamsten, Anders (58) (59)
Hocking, Lynne J (36) (93)
Huang, Jie (95)
Hung, Joseph (27) (96)
Ingelsson, Erik (98) (99)
James, Alan L (27) (77) (96)
Jarvelin, Marjo-Riitta (100) (101) (102)
Juonala, Markus (103) (104)
Kähönen, Mika (45) (97)
Koistinen, Heikki A (38) (106) (107)
Kuusisto, Johanna (110) (111)
Lakka, Timo A. (40) (57)
Lind, Lars (99)
Linneberg, Allan (10) (114) (115)
Loh, Marie (72) (116)
Lubke, Gitta (118)
McKnight, Barbara (29) (74)
Musk, AW (Bill) (27) (77) (96)
Pisinger, Charlotta (10) (115)
Raitakari, Olli T. (103) (104)
Rao, D. C. (60)
Sennblad, Bengt (58) (59)
Staessen, Jan A. (127) (128) (129)
Taylor, Kent D (130) (131)
Thorand, Barbara (52) (90)
Tuomilehto, Jaakko (133) (134) (135)
Wong, Andrew (136)
Zhao, Wei (25)
Cucca, Francesco (89) (124)
Cusi, Daniele (142) (143)
Franks, Paul W. (19) (20) (22)
Froguel, Philippe (26) (102)
Grabe, Hans Jörgen (62) (144)
Wouter Jukema, J (63) (145) (146)
Kooner, Jaspal S. (73) (84) (102)
Kuh, Diana (136)
Laakso, Markku (110) (111)
März, Winfried (126) (147)
McCarthy, Mark I. (18) (34) (148)
Morris, Andrew P. (18) (149)
Peters, Annette (52) (90)
Polasek, Ozren (36) (108)
Psaty, Bruce M (29) (151)
Qi, Lu (22) (152)
Rauramaa, Rainer (40) (111)
Smith, Blair H. (36) (153)
Sørensen, Thorkild I A (10) (154) (155)
Strauch, Konstantin (52) (119)
Tremoli, Elena (28) (137)
van der Harst, Pim (65) (68) (146)
Barroso, Inês (95) (117) (157)
Deloukas, Panagiotis (37) (95) (135)
Hirschhorn, Joel N (22) (66) (67)
Hunter, David J. (12) (22) (67)
van Duijn, Cornelia M. (24) (158) (159)
Heid, Iris M (2) (52)
Loos, Ruth J F (23) (44)
Kilpeläinen, Tuomas O. (10) (23) (44)
Cupples, L Adrienne * (5) (11)

* Corresponding author

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  1. (1) University of North Carolina System, grid.410711.2
  2. (2) University of Regensburg, grid.7727.5
  3. (3) 63108, St. Louis, Missouri, USA
  4. (4) Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine
  5. (5) Boston University, grid.189504.1
  6. (6) TransMed Systems, Inc., 95014, Cupertino, California, USA
  7. (7) Population Health Research Institute, St. George's, University of London, SW17 0RE, London, UK
  8. (8) Johns Hopkins University, grid.21107.35
  9. (9) Steno Diabetes Center, grid.419658.7, Capital Region
  10. (10) University of Copenhagen, grid.5254.6, KU
  11. (11) NHLBI Framingham Heart Study, 01702, Framingham, Massachusetts, USA
  12. (12) Brigham and Women's Hospital, grid.62560.37
  13. (13) Boston University School of Medicine, grid.475010.7
  14. (14) National Heart Lung and Blood Institute, grid.279885.9
  15. (15) Institute of Social and Preventive Medicine, grid.482968.9
  16. (16) Swiss instititute of Bioinformatics
  17. (17) University of Lausanne, grid.9851.5
  18. (18) Wellcome Centre for Human Genetics, grid.270683.8
  19. (19) Umeå University, grid.12650.30
  20. (20) Lund University, grid.4514.4
  21. (21) Albert Einstein College of Medicine, grid.251993.5
  22. (22) Harvard University, grid.38142.3c
  23. (23) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  24. (24) Erasmus University Medical Center, grid.5645.2
  25. (25) University of Michigan, grid.214458.e
  26. (26) Pasteur Institute of Lille, grid.8970.6
  27. (27) University of Western Australia, grid.1012.2
  28. (28) University of Milan, grid.4708.b
  29. (29) University of Washington, grid.34477.33
  30. (30) Dokuz Eylül University, grid.21200.31
  31. (31) University of Gothenburg, grid.8761.8
  32. (32) University of Tartu, grid.10939.32
  33. (33) University Hospital Regensburg, grid.411941.8
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  35. (35) National University of Singapore, grid.4280.e
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  38. (38) National Institute for Health and Welfare, grid.14758.3f
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  40. (40) Kuopion Liikuntalääketieteen Tutkimuslaitos, grid.419013.e
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  43. (43) University of Hawaii at Manoa, grid.410445.0
  44. (44) Institute of Metabolic Science, grid.470900.a
  45. (45) Tampere University, grid.502801.e
  46. (46) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  47. (47) King's College London, grid.13097.3c
  48. (48) University of Virginia, grid.27755.32
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  50. (50) Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, D-81377, Munich, Germany
  51. (51) German Centre for Cardiovascular Research, grid.452396.f
  52. (52) Helmholtz Zentrum München, grid.4567.0
  53. (53) Laval University, grid.23856.3a
  54. (54) Department of Social and Health Care, City of Helsinki, Helsinki, Finland
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  60. (60) Washington University in St. Louis, grid.4367.6
  61. (61) National Institute on Aging, grid.419475.a
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  63. (63) Leiden University Medical Center, grid.10419.3d
  64. (64) University Medical Center Utrecht, grid.7692.a
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  66. (66) Boston Children's Hospital, grid.2515.3
  67. (67) Broad Institute, grid.66859.34
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  72. (72) Dept Epidemiology and Biostatistics, School of Public Health, Imperical College London, UK
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  74. (74) Fred Hutchinson Cancer Research Center, grid.270240.3
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  81. (81) National Human Genome Research Institute, grid.280128.1
  82. (82) University College Cork, grid.7872.a
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  84. (84) Imperial College Healthcare NHS Trust, grid.417895.6
  85. (85) EMGO+ Institute Vrije Universiteit & Vrije Universiteit Medical Center
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  89. (89) University of Sassari, grid.11450.31
  90. (90) German Center for Diabetes Research, grid.452622.5
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  92. (92) Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  105. (105) Department of Orthopedics and Clinical Sciences, Clinical and Molecular Osteoporosis Research Unit, Skåne University Hospital, Lund University, Malmö, Sweden
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  133. (133) Danube University Krems, grid.15462.34
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  158. (158) Center for Medical Systems Biology, Leiden, The Netherlands
  159. (159) Netherlands Consortium for Healthy Ageing, grid.452197.c

Description

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

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University of Copenhagen

Danish Open Access Indicator

2017: Realized

Research area: Social Sciences

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2017: Level 2

Research area: Social Sciences

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Times Cited: 80

Field Citation Ratio (FCR): 16.81

Relative Citation ratio (RCR): 5.72

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