Genome-Wide and Candidate Gene Association Study of Cigarette Smoking Behaviors

被引:196
作者
Caporaso, Neil [1 ]
Gu, Fangyi [2 ]
Chatterjee, Nilanjan [1 ]
Jin Sheng-Chih [3 ]
Yu, Kai [1 ]
Yeager, Meredith [1 ,5 ]
Chen, Constance [2 ]
Jacobs, Kevin [5 ,6 ]
Wheeler, William [7 ]
Landi, Maria Teresa [1 ]
Ziegler, Regina G. [1 ]
Hunter, David J. [1 ,2 ,5 ]
Chanock, Stephen [4 ]
Hankinson, Susan [2 ]
Kraft, Peter [2 ]
Bergen, Andrew W. [8 ]
机构
[1] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
[2] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA USA
[3] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA
[4] Brigham and Womens Hosp, Channing Lab, Boston, MA USA
[5] NCI, NIH, Advanced Technol Ctr, Core Genotyping Facil, Gaithersburg, MD USA
[6] BioInformed LLC, Gaithersburg, MD USA
[7] Informat Management Serv, Inc, Rockville, MD USA
[8] SRI Int, Ctr Hlth Sci, Mol Genet Program, Menlo Pk, CA USA
来源
PLOS ONE | 2009年 / 4卷 / 02期
关键词
SEROTONIN TRANSPORTER GENE; NICOTINE REPLACEMENT THERAPY; MONOAMINE-OXIDASE; LINKAGE SCAN; LUNG-CANCER; SUSCEPTIBILITY LOCUS; QUANTITATIVE TRAIT; AFRICAN-AMERICANS; CYP2A6; GENOTYPE; RECEPTOR GENES;
D O I
10.1371/journal.pone.0004653
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS) performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO) Trial, and 2,282 women from the Nurses' Health Study (NHS). We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years), and three binary (ever versus never smoking, <= 10 versus >10 cigarettes per day [CPDBI], and current versus former smoking). Association testing for each single nucleotide polymorphism (SNP) was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10(-7)) in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10(-5) for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10(-3)), including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4x10(-5)), our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.
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页数:10
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