> Details
Saccone, Nancy L.
[Author];
Culverhouse, Robert C.
[Author];
Kong, Xiangyang
[Author];
Landi, Maria Teresa
[Author];
Ma, Jennie Z.
[Author];
Short, Susan E.
[Author];
Stephens, Sarah H.
[Author];
Stevens, Victoria L.
[Author];
Sun, Lingwei
[Author];
Wang, Yufei
[Author];
Wenzlaff, Angela S.
[Author];
Aggen, Steven H.
[Author];
Schwantes-An, Tae-Hwi
[Author];
Breslau, Naomi
[Author];
Broderick, Peter
[Author];
Chatterjee, Nilanjan
[Author];
Chen, Jingchun
[Author];
Heath, Andrew C.
[Author];
Heliövaara, Markku
[Author];
Hoft, Nicole R.
[Author];
Hunter, David J.
[Author];
Jensen, Majken K.
[Author];
Martin, Nicholas G.
[Author];
Cannon, Dale S.
[Author];
[...]
Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
Sharing
Reference
management
Direct link
Bookmarks
Remove from
bookmarks
Share this by email
Share this on Twitter
Share this on Facebook
Share this on Whatsapp
- Media type: E-Article
- Title: Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD
- Contributor: Saccone, Nancy L. [Author]; Culverhouse, Robert C. [Author]; Kong, Xiangyang [Author]; Landi, Maria Teresa [Author]; Ma, Jennie Z. [Author]; Short, Susan E. [Author]; Stephens, Sarah H. [Author]; Stevens, Victoria L. [Author]; Sun, Lingwei [Author]; Wang, Yufei [Author]; Wenzlaff, Angela S. [Author]; Aggen, Steven H. [Author]; Schwantes-An, Tae-Hwi [Author]; Breslau, Naomi [Author]; Broderick, Peter [Author]; Chatterjee, Nilanjan [Author]; Chen, Jingchun [Author]; Heath, Andrew C. [Author]; Heliövaara, Markku [Author]; Hoft, Nicole R. [Author]; Hunter, David J. [Author]; Jensen, Majken K. [Author]; Martin, Nicholas G. [Author]; Cannon, Dale S. [Author]; [...]
-
Published:
Public Library of Science, 2010
- Published in: PLoS Genetics 6(8), e1001053 - (2010). doi:10.1371/journal.pgen.1001053
- Language: English
- DOI: https://doi.org/10.1371/journal.pgen.1001053
- ISSN: 1553-7390; 1553-7404
- Origination:
-
Footnote:
Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen.
- Description: Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10−35 and <10−8 respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10−6). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10−20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves ...
- Access State: Open Access