Abstract
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 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 (odds ratio [OR] = 1.33, 95% CI = 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.
| Original language | English |
|---|---|
| Pages (from-to) | 340-351 |
| Number of pages | 12 |
| Journal | Genetic Epidemiology |
| Volume | 36 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - May 2012 |
| Externally published | Yes |
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Keywords
- Cross-population
- Genetics
- Meta-analysis
- Smoking
ASJC Scopus subject areas
- Epidemiology
- Medicine(all)
- Genetics(clinical)
Cite this
Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25. / Chen, Li Shiun; Saccone, Nancy L.; Culverhouse, Robert C.; Bracci, Paige M.; Chen, Chien Hsiun; Dueker, Nicole; Han, Younghun; Huang, Hongyan; Jin, Guangfu; Kohno, Takashi; Ma, Jennie Z.; Przybeck, Thomas R.; Sanders, Alan R.; Smith, Jennifer A.; Sung, Yun Ju; Wenzlaff, Angie S.; Wu, Chen; Yoon, Dankyu; Chen, Ying Ting; Cheng, Yu Ching; Cho, Yoon Shin; David, Sean P.; Duan, Jubao; Eaton, Charles B.; Furberg, Helena; Goate, Alison M.; Gu, Dongfeng; Hansen, Helen M.; Hartz, Sarah; Hu, Zhibin; Kim, Young Jin; Kittner, Steven J.; Levinson, Douglas F.; Mosley, Thomas H.; Payne, Thomas J.; Rao, D. C.; Rice, John P.; Rice, Treva K.; Schwantes-An, Tae Hwi; Shete, Sanjay S.; Shi, Jianxin; Spitz, Margaret R.; Sun, Yan V.; Tsai, Fuu Jen; Wang, Jen C.; Wrensch, Margaret R.; Xian, Hong; Gejman, Pablo V.; He, Jiang; Hunt, Steven; Kardia, Sharon L.; Li, Ming D.; Lin, Dongxin; Mitchell, Braxton D.; Park, Taesung; Schwartz, Ann G.; Shen, Hongbing; Wiencke, John K.; Wu, Jer Yuarn; Yokota, Jun; Amos, Christopher I.; Bierut, Laura J.
In: Genetic Epidemiology, Vol. 36, No. 4, 05.2012, p. 340-351.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25
AU - Chen, Li Shiun
AU - Saccone, Nancy L.
AU - Culverhouse, Robert C.
AU - Bracci, Paige M.
AU - Chen, Chien Hsiun
AU - Dueker, Nicole
AU - Han, Younghun
AU - Huang, Hongyan
AU - Jin, Guangfu
AU - Kohno, Takashi
AU - Ma, Jennie Z.
AU - Przybeck, Thomas R.
AU - Sanders, Alan R.
AU - Smith, Jennifer A.
AU - Sung, Yun Ju
AU - Wenzlaff, Angie S.
AU - Wu, Chen
AU - Yoon, Dankyu
AU - Chen, Ying Ting
AU - Cheng, Yu Ching
AU - Cho, Yoon Shin
AU - David, Sean P.
AU - Duan, Jubao
AU - Eaton, Charles B.
AU - Furberg, Helena
AU - Goate, Alison M.
AU - Gu, Dongfeng
AU - Hansen, Helen M.
AU - Hartz, Sarah
AU - Hu, Zhibin
AU - Kim, Young Jin
AU - Kittner, Steven J.
AU - Levinson, Douglas F.
AU - Mosley, Thomas H.
AU - Payne, Thomas J.
AU - Rao, D. C.
AU - Rice, John P.
AU - Rice, Treva K.
AU - Schwantes-An, Tae Hwi
AU - Shete, Sanjay S.
AU - Shi, Jianxin
AU - Spitz, Margaret R.
AU - Sun, Yan V.
AU - Tsai, Fuu Jen
AU - Wang, Jen C.
AU - Wrensch, Margaret R.
AU - Xian, Hong
AU - Gejman, Pablo V.
AU - He, Jiang
AU - Hunt, Steven
AU - Kardia, Sharon L.
AU - Li, Ming D.
AU - Lin, Dongxin
AU - Mitchell, Braxton D.
AU - Park, Taesung
AU - Schwartz, Ann G.
AU - Shen, Hongbing
AU - Wiencke, John K.
AU - Wu, Jer Yuarn
AU - Yokota, Jun
AU - Amos, Christopher I.
AU - Bierut, Laura J.
PY - 2012/5
Y1 - 2012/5
N2 - 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 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 (odds ratio [OR] = 1.33, 95% CI = 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.
AB - 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 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 (odds ratio [OR] = 1.33, 95% CI = 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.
KW - Cross-population
KW - Genetics
KW - Meta-analysis
KW - Smoking
UR - http://www.scopus.com/inward/record.url?scp=84860333167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860333167&partnerID=8YFLogxK
U2 - 10.1002/gepi.21627
DO - 10.1002/gepi.21627
M3 - Article
VL - 36
SP - 340
EP - 351
JO - Genetic Epidemiology
JF - Genetic Epidemiology
SN - 0741-0395
IS - 4
ER -