TY - JOUR
T1 - Haplotypes with Copy Number and Single Nucleotide Polymorphisms in CYP2A6 Locus Are Associated with Smoking Quantity in a Japanese Population
AU - Kumasaka, Natsuhiko
AU - Aoki, Masayuki
AU - Okada, Yukinori
AU - Takahashi, Atsushi
AU - Ozaki, Kouichi
AU - Mushiroda, Taisei
AU - Hirota, Tomomitsu
AU - Tamari, Mayumi
AU - Tanaka, Toshihiro
AU - Nakamura, Yusuke
AU - Kamatani, Naoyuki
AU - Kubo, Michiaki
N1 - Funding Information:
We thank all technical staff of BioBank Japan Project and Laboratory for Genotyping Development at RIKEN for SNP genotyping. This work was conducted as a part of the BioBank Japan Project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government.
PY - 2012/9/25
Y1 - 2012/9/25
N2 - Smoking is a major public health problem, but the genetic factors associated with smoking behaviors are not fully elucidated. Here, we have conducted an integrated genome-wide association study to identify common copy number polymorphisms (CNPs) and single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) in Japanese smokers (N = 17,158). Our analysis identified a common CNP with a strong effect on CPD (rs8102683; P = 3.8 × 10-42) in the 19q13 region, encompassing the CYP2A6 locus. After adjustment for the associated CNP, we found an additional associated SNP (rs11878604; P = 9.7 × 10-30) located 30 kb downstream of the CYP2A6 gene. Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA F-test P = 9.5 × 10-52). These haplotypes were also associated with smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease and arteriosclerosis obliterans.
AB - Smoking is a major public health problem, but the genetic factors associated with smoking behaviors are not fully elucidated. Here, we have conducted an integrated genome-wide association study to identify common copy number polymorphisms (CNPs) and single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) in Japanese smokers (N = 17,158). Our analysis identified a common CNP with a strong effect on CPD (rs8102683; P = 3.8 × 10-42) in the 19q13 region, encompassing the CYP2A6 locus. After adjustment for the associated CNP, we found an additional associated SNP (rs11878604; P = 9.7 × 10-30) located 30 kb downstream of the CYP2A6 gene. Imputation of the CYP2A6 locus revealed that haplotypes underlying the CNP and the SNP corresponded to classical, functional alleles of CYP2A6 gene that regulate nicotine metabolism and explained 2% of the phenotypic variance of CPD (ANOVA F-test P = 9.5 × 10-52). These haplotypes were also associated with smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease and arteriosclerosis obliterans.
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U2 - 10.1371/journal.pone.0044507
DO - 10.1371/journal.pone.0044507
M3 - Article
C2 - 23049750
AN - SCOPUS:84866691284
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 9
M1 - e44507
ER -
