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Translational Psychiatry - Genome-wide meta-analyses of smoking behaviors in African Americans

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Translational Psychiatry - Genome-wide meta-analyses of smoking behaviors in African Americans

Original Article

Citation: Translational Psychiatry (2012) 2, e119; doi:10.1038/tp.2012.41
Published online 22 May 2012

Genome-wide meta-analyses of smoking behaviors in African Americans

S P David1,2,3, A Hamidovic4,51, G K Chen5,51, A W Bergen1, J Wessel1,6,7, J L Kasberger8, W M Brown9, S Petruzella10, E L Thacker11, Y Kim12, M A Nalls13, G J Tranah14, Y J Sung15, C B Ambrosone16, D Arnett17, E V Bandera18, D M Becker19, L Becker19, S I Berndt20, L Bernstein21, W J Blot22,23, U Broeckel24, S G Buxbaum25, N Caporaso20, G Casey5, S J Chanock20, S L Deming23, W R Diver26, C B Eaton3, D S Evans14, M K Evans27, M Fornage28, N Franceschini29, T B Harris30, B E Henderson5, D G Hernandez13, B Hitsman4, J J Hu31, S C Hunt32, S A Ingles5, E M John33,34, R Kittles35, S Kolb36, L N Kolonel37, L Le Marchand37, Y Liu38, K K Lohman9, B McKnight39, R C Millikan40, A Murphy41, C Neslund-Dudas42, S Nyante40, M Press5, B M Psaty43,44, D C Rao15, S Redline45, J L Rodriguez-Gil31, B A Rybicki42, L B Signorello22,23, A B Singleton13, J Smoller46, B Snively9, B Spring4, J L Stanford36, S S Strom47, G E Swan1, K D Taylor48, M J Thun26, A F Wilson12, J S Witte49, Y Yamamura47, L R Yanek19, K Yu20, W Zheng23, R G Ziegler20, A B Zonderman50, E Jorgenson8,52, C A Haiman5,52 and H Furberg10,52
  1. 1Center for Health Sciences, Policy Division, SRI International, Menlo Park, CA, USA
  2. 2Center for Education and Research in Family and Community Medicine, Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, CA, USA
  3. 3Department of Family Medicine, Center for Primary Care and Prevention, Brown Alpert Medical School, Pawtucket, RI, USA
  4. 4Department of Preventative Medicine, Northwestern University, Chicago, IL, USA
  5. 5Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  6. 6Department of Public Health, Division of Epidemiology and Environmental Health, Indiana University School of Medicine, Indianapolis, IN, USA
  7. 7Department of Medicine, Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA
  8. 8Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA, USA
  9. 9Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
  10. 10Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  11. 11Department of Epidemiology, University of Washington, Seattle, WA, USA
  12. 12Genometrics Section, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA
  13. 13Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
  14. 14California Pacific Medical Center Research Institute, San Francisco, CA, USA
  15. 15Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA
  16. 16Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
  17. 17Department of Epidemiology, University of Alabama, Birmingham, AL, USA
  18. 18The Cancer Institute of New Jersey, New Brunswick, NJ, USA
  19. 19Department of Medicine, The Johns Hopkins GeneSTAR Research Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  20. 20Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  21. 21Department of Population Science, Division of Cancer Etiology, Beckman Research Institute, City of Hope, Duarte, CA, USA
  22. 22International Epidemiology Institute, Rockville, MD, USA
  23. 23Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University and the Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
  24. 24Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
  25. 25Jackson Heart Study, Jackson State University, Jackson, MS, USA
  26. 26Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
  27. 27Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
  28. 28Division of Epidemiology, Brown Foundation Institute of Molecular Medicine, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
  29. 29Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  30. 30Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA
  31. 31Department of Epidemiology and Public Health, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
  32. 32Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
  33. 33Cancer Prevention Institute of California, Fremont, CA, USA
  34. 34Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA, USA
  35. 35Department of Medicine, Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA
  36. 36Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  37. 37Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, HI, USA
  38. 38Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  39. 39Department of Biostatistics, University of Washington, Seattle, WA, USA
  40. 40Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
  41. 41Department of Urology, Northwestern University, Chicago, IL, USA
  42. 42Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA
  43. 43Departments of Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, USA
  44. 44Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
  45. 45Department of Medicine and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
  46. 46Department of Psychiatry, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  47. 47Department of Epidemiology, The University of Texas MD, Anderson Cancer Center, Houston, TX, USA
  48. 48Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
  49. 49Departments of Epidemiology and Biostatistics, and Urology, Institute for Human Genetics, University of California, San Francisco, CA, USA
  50. 50Laboratory of Personality and Cognition, National Institute on Aging, National Institutes of Health, Baltimore, MD
Correspondence: Dr SP David, Center for Education and Research in Family and Community Medicine, Division of General Medical Disciplines, Stanford University School of Medicine, 1215 Welch Road, Modular G, Stanford, CA 93405-5408, USA. E-mail: spdavid@stanford.edu; CA Haiman, Department of Preventive Medicine, University of Southern California Keck School of Medicine, Harlyne Norris Research Tower, 1450 Biggy Street, Room 1504A, Los Angeles, CA 90033, USA. E-mail: haiman@usc.edu; E Jorgenson, Enest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, San Francisco, CA 94608, USA. E-mail: ejorgenson@gallo.ucsf.edu
51Joint first authors.
52Joint senior authors.
Received 13 March 2012; Accepted 10 April 2012
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Abstract

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n=32389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β=0.040, s.e.=0.007, P=1.84 × 10−8). This variant is present in the 5′-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Keywords:

African American; genome-wide association; health disparities; nicotine; smoking; tobacco

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