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 David^1,2,3, A Hamidovic^4,51, G K Chen^5,51, A W Bergen¹, J Wessel^1,6,7, 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 Blot^22,23, 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 John^33,34, 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 Psaty^43,44, D C Rao¹⁵, S Redline⁴⁵, J L Rodriguez-Gil³¹, B A Rybicki⁴², L B Signorello^22,23, 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 Jorgenson^8,52, C A Haiman^5,52 and H Furberg^10,52

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=32 389). 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