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GWAS Study

Haplotypes with copy number and single nucleotide polymorphisms in CYP2A6 locus are associated with smoking quantity in a Japanese population.

Kumasaka N, Aoki M, Okada Y et al.

23049750 PubMed ID
GWAS Study Type
17158 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

KN
Kumasaka N
AM
Aoki M
OY
Okada Y
TA
Takahashi A
OK
Ozaki K
MT
Mushiroda T
HT
Hirota T
TM
Tamari M
TT
Tanaka T
NY
Nakamura Y
KN
Kamatani N
KM
Kubo M
Chapter II

Abstract

Summary of the research findings

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 x 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 x 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 x 10(-52)). These haplotypes were also associated with smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease and arteriosclerosis obliterans.

11,696 Japanese ancestry smokers

Chapter III

Study Statistics

Key metrics and study information

17158
Total Participants
GWAS
Study Type
Yes
Replicated
5,462 Japanese ancestry smokers
Replication Participants
East Asian
Ancestry
Japan
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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