Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25

Li-Shiun Chen; Nicole Dueker; Nancy L Saccone; Jer-Yuarn Wu; Robert C Culverhouse; Paige M Bracci; Chien-Hsiun Chen; 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; Jun Yokota; Christopher I Amos; Laura J Bierut

doi:10.1002/gepi.21627

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Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25

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Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25

Li-Shiun Chen, Nicole Dueker, Nancy L Saccone, Jer-Yuarn Wu, Robert C Culverhouse, Paige M Bracci, Chien-Hsiun Chen, Younghun Han, Hongyan Huang, Guangfu Jin, …

Genetic epidemiology, Vol.36(4), pp.340-351

2012-05

DOI: https://doi.org/10.1002/gepi.21627

PMCID: PMC3387741

PMID: 22539395

Abstract

meta-analysis

cross-population

smoking

Genetics

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 (CPD) 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 (OR=1.33, 95%C.I.=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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.5 Neuroscience; 1.5.894 Nicotine
Web Of Science research areas: Genetics & Heredity; Mathematical & Computational Biology
ESI research areas: Molecular Biology & Genetics

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Title: Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25
Creators: Li-Shiun Chen - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Nicole Dueker - Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland, United States of America
Nancy L Saccone - Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Jer-Yuarn Wu - National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Robert C Culverhouse - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
Paige M Bracci - Department of Epidemiology and Biostatistics, UCSF, San Francisco, California, United States of America
Chien-Hsiun Chen - National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Younghun Han - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Hongyan Huang - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Guangfu Jin - Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
Takashi Kohno - Division of Genome Biology, National Cancer Center Research Institute 1-1, Tokyo, Japan
Jennie Z Ma - Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States of America
Thomas R Przybeck - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Alan R Sanders - Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, and University of Chicago, Chicago, Illinois, United States of America
Jennifer A Smith - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America
Yun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Angie S Wenzlaff - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America
Chen Wu - Department of Etiology & Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
Dankyu Yoon - Interdisciplinary Program in Bioinformatics, College of Natural Science, Seoul National University, Seoul, Korea
Ying-Ting Chen - National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Yu-Ching Cheng - Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland, United States of America
Yoon Shin Cho - Center for Genome Science, National Institute of Health, Seoul, Korea
Sean P David - Center for Health Sciences, SRI International, Menlo Park, California, United States of America
Jubao Duan - Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, and University of Chicago, Chicago, Illinois, United States of America
Charles B Eaton - Department of Family Medicine, Brown University, Providence, Rhode Island, United States of America
Helena Furberg - Department of Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
Alison M Goate - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Dongfeng Gu - Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Helen M Hansen - Neurological Surgery, Division of Epidemiology, Helen Diller Family Cancer Center, San Francisco, California, United States of America
Sarah Hartz - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Zhibin Hu - Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
Young Jin Kim - Interdisciplinary Program in Bioinformatics, College of Natural Science, Seoul National University, Seoul, Korea
Steven J Kittner - Department of Neurology, University of Maryland, Baltimore, Maryland, United States of America
Douglas F Levinson - Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, United States of America
Thomas H Mosley - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America
Thomas J Payne - University of Mississippi Medical Center, Jackson, Mississippi, United States of America
D C Rao - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
John P Rice - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Treva K Rice - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Tae-Hwi Schwantes-An - Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America
Sanjay S Shete - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Jianxin Shi - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
Margaret R Spitz - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Yan V Sun - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America
Fuu-Jen Tsai - School of Post-Baccalaureate Chinese Medicine, China Medical University, Taiwan
Jen C Wang - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Margaret R Wrensch - Neurological Surgery, Division of Epidemiology, Helen Diller Family Cancer Center, San Francisco, California, United States of America
Hong Xian - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
Pablo V Gejman - Department of Psychiatry and Behavioral Sciences, North Shore University Health System Research Institute, and University of Chicago, Chicago, Illinois, United States of America
Jiang He - Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America
Steven C Hunt - Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America
Sharon L Kardia - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America
Ming D Li - Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, United States of America
Dongxin Lin - Department of Etiology & Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
Braxton D Mitchell - Center for Genome Science, National Institute of Health, Seoul, Korea
Taesung Park - Department of Statistics, College of Natural Science, Seoul National University, Seoul, Korea
Ann G Schwartz - Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America
Hongbing Shen - Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
John K Wiencke - Neurological Surgery, Division of Epidemiology, Helen Diller Family Cancer Center, San Francisco, California, United States of America
Jun Yokota - Division of Multistep Carcinogenesis, National Cancer Center Research Institute 1-1, Tokyo, Japan
Christopher I Amos - Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America
Laura J Bierut - Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
Publication Details: Genetic epidemiology, Vol.36(4), pp.340-351
Grant note: R01 ES006717 || ES / National Institute of Environmental Health Sciences : NIEHS R01 HL068737 || HL / National Heart, Lung, and Blood Institute : NHLBI U10 HL054497 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 WH032119 || WH / Women's Health Initiative : WHI R01 CA127219 || CA / National Cancer Institute : NCI U01 MH046318-08 || MH / National Institute of Mental Health : NIMH N01 WH032122 || WH / Women's Health Initiative : WHI U01 HG004402 || HG / National Human Genome Research Institute : NHGRI U10 HL054496 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 MH059566 || MH / National Institute of Mental Health : NIMH R01 CA087895 || CA / National Cancer Institute : NCI N01 HC055015 || HC / Division of Epidemiology & Clinical Applications : NHLBI U01 HL072507 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 MH059565 || MH / National Institute of Mental Health : NIMH N01 WH032105 || WH / Women's Health Initiative : WHI U10 HL054495 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 WH042129 || WH / Women's Health Initiative : WHI N01 HC055019 || HC / Division of Epidemiology & Clinical Applications : NHLBI N01PC35145 || CA / National Cancer Institute : NCI R01 DA017441 || DA / National Institute on Drug Abuse : NIDA R01 NS045012 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 MH060879 || MH / National Institute of Mental Health : NIMH R01 CA055769 || CA / National Cancer Institute : NCI R01 MH081800 || MH / National Institute of Mental Health : NIMH U01 HG004422 || HG / National Human Genome Research Institute : NHGRI R01 DA026911 || DA / National Institute on Drug Abuse : NIDA U01 NS069208 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 MH067257 || MH / National Institute of Mental Health : NIMH K02 DA021237 || DA / National Institute on Drug Abuse : NIDA R01 CA052689 || CA / National Cancer Institute : NCI N01 WH032111 || WH / Women's Health Initiative : WHI U01 MH079470 || MH / National Institute of Mental Health : NIMH U01 MH046276-08 || MH / National Institute of Mental Health : NIMH U01 HL054457 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 MH059587 || MH / National Institute of Mental Health : NIMH R21 DA027331 || DA / National Institute on Drug Abuse : NIDA R01 CA121197 || CA / National Cancer Institute : NCI N01HC55022 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 HC055016 || HC / Division of Epidemiology & Clinical Applications : NHLBI U01 MH046289-08 || MH / National Institute of Mental Health : NIMH N01 WH042107 || WH / Women's Health Initiative : WHI U10 HL054515 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 WH032100 || WH / Women's Health Initiative : WHI R01 MH059588 || MH / National Institute of Mental Health : NIMH P30 DK072488 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK KL2 RR024994 || RR / National Center for Research Resources : NCRR P01 CA089392 || CA / National Cancer Institute : NCI R01 MH061675 || MH / National Institute of Mental Health : NIMH R01 CA133996 || CA / National Cancer Institute : NCI R01 MH060870 || MH / National Institute of Mental Health : NIMH N01 HC055021 || HC / Division of Epidemiology & Clinical Applications : NHLBI K08 DA030398 || DA / National Institute on Drug Abuse : NIDA R01 HL059367 || HL / National Heart, Lung, and Blood Institute : NHLBI U19 CA148127 || CA / National Cancer Institute : NCI R01 MH059571 || MH / National Institute of Mental Health : NIMH U10 HL054473 || HL / National Heart, Lung, and Blood Institute : NHLBI UL1 RR025005 || RR / National Center for Research Resources : NCRR U01 HG004436 || HG / National Human Genome Research Institute : NHGRI U10 HL054472 || HL / National Heart, Lung, and Blood Institute : NHLBI U01 MH079469 || MH / National Institute of Mental Health : NIMH R21 DA033827 || DA / National Institute on Drug Abuse : NIDA R01 CA060691 || CA / National Cancer Institute : NCI U01 HG004446 || HG / National Human Genome Research Institute : NHGRI R01 MH059586 || MH / National Institute of Mental Health : NIMH R03 DA023166 || DA / National Institute on Drug Abuse : NIDA R01 DA012844 || DA / National Institute on Drug Abuse : NIDA N01 WH022110-024 || WH / Women's Health Initiative : WHI U54 RR020278 || RR / National Center for Research Resources : NCRR R01 HL087660 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 WH032108 || WH / Women's Health Initiative : WHI N01 WH32115 || WH / Women's Health Initiative : WHI N01 WH024152 || WH / Women's Health Initiative : WHI U10 HL054509 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 CA141716 || CA / National Cancer Institute : NCI P50 CA070907 || CA / National Cancer Institute : NCI N01 HC055020 || HC / Division of Epidemiology & Clinical Applications : NHLBI N01 WH044221 || WH / Women's Health Initiative : WHI U10 HL054471 || HL / National Heart, Lung, and Blood Institute : NHLBI N01 WH032118 || WH / Women's Health Initiative : WHI N01 HC055018 || HC / Division of Epidemiology & Clinical Applications : NHLBI R01 HL086694 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL087641 || HL / National Heart, Lung, and Blood Institute : NHLBI
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 22539395
PMCID: PMC3387741
Record Identifier: 991031600647202976