Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25
Year: 2012
Type: article
Abstract: Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.
Source: Genetic Epidemiology
DOI: 10.1002/gepi.21627
Authors: Li‐Shiun Chen, Nancy L. Saccone, Robert C. Culverhouse, Paige M. Bracci, Chien‐Hsiun Chen, Nicole Dueker, Younghun Han, Hongyan Huang, Guangfu Jin, Takashi Kohno, Jennie Z. Ma, Thomas R. Przybeck, Alan R. Sanders, Jennifer A. Smith, Yun Ju Sung, Angie S. Wenzlaff, Chen Wu, Dankyu Yoon, Ying‐Ting Chen, Yu‐Ching Cheng, Yoon Shin Cho, Sean P. David, Jubao Duan, Charles B. Eaton, Helena Furberg, Alison M. Goate, Dongfeng Gu, Helen M. Hansen, Sarah Hartz, Zhibin Hu, Young Jin Kim, Steven J. Kittner, Douglas F. Levinson, Thomas H. Mosley, Thomas J. Payne, D. C. Rao, John P. Rice, Treva K. Rice, Tae‐Hwi Schwantes‐An, Sanjay S. Shete, Jianxin Shi, Margaret R. Spitz, Yan V. Sun, Fuu‐Jen Tsai, Jen C. Wang, Margaret R. Wrensch, Hong Xian, Pablo V. Gejman, Jiang He, Steven C. Hunt, Sharon L. Kardia, Ming D. Li, Dongxin Lin, Braxton D. Mitchell, Taesung Park, Ann G. Schwartz, Hongbing Shen, John K. Wiencke, Jer‐Yuarn Wu, Jun Yokota, Christopher I. Amos, Laura J. Bierut
Institutions: Washington University in St. Louis, University of California, San Francisco, China Medical University, Institute of Biomedical Sciences, Academia Sinica, Academia Sinica, University of Maryland, Baltimore, The University of Texas MD Anderson Cancer Center, Nanjing Medical University, National Cancer Center Research Institute, University of Virginia, University of Chicago, University of Michigan, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Seoul National University, Korea National Institute of Health, University of Maryland Medical Center, Hallym University, SRI International, Brown University, Stanford Medicine, Stanford University, Memorial Sloan Kettering Cancer Center, Fu Wai Hospital, UCSF Helen Diller Family Comprehensive Cancer Center, University of Mississippi Medical Center, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Tulane University, University of Utah
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, Cancer Prevention and Research Institute of Texas, Office of Research and Development, Wayne State University, University of Minnesota, Tulane University, Johns Hopkins University, Broad Institute, Barbara Ann Karmanos Cancer Institute, National Research Foundation, National Science Council, Academia Sinica, Zhengzhou University, Chinese Academy of Medical Sciences, Nanjing University, Shandong Academy of Medical Sciences, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Public Health Service, University of Texas MD Anderson Cancer Center, Korea National Institute of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources, NIH Clinical Center, Office of Research on Women's Health
Awards: G1034519783, G1043272518, G1054787755, G105512408, G10598100, G1080192134, G109231058, G1107292973, Women's Health Initiative, G111615301, HYPERGEN, G118440752, G122526512, G1270179341, G1272326107, G1305265183, G1311563309, G1325221871, Women's Health Initiative, G1360749331, G136105103, G1374583558, Exploratory/Developmental Study of Pharmacogenetic Smoking Cessation Therapy, G1509419569, G1567724564, G156924709, Women's Health Initiative, G1593340546, G1617453120, G1646017446, G1658243001, G1691445938, G1730664372, G174366600, G1767672275, G1794460117, G1828710530, Genetic Epidemiology of Lung Cancer, G187063468, G1881788261, G1910965489, G1946071602, G2016628173, G203315901, G206718646, G2076123899, G2081319657, Atherosclerosis Risk in Communities Study (ARIC), Women's Health Initiative, G2146332128, G2149630760, G215333750, G2171212234, G2189639697, G2242747391, G2244524868, G2252333647, G2253702613, G2295046671, G2417273319, G2447083100, G2449723990, G247409761, CCSP 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OpenAlex ID: W2114201773