Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25

Li Shiun Chen, Nancy L. Saccone, Robert C. Culverhouse, Paige M. Bracci, Chien Hsiun Chen, Nicole Dueker, Younghun Han, Hongyan Huang, Guangfu Jin, Takashi Kohno, Jennie Z. Ma, Thomas R. Przybeck, Alan R. Sanders, Jennifer A. Smith, Yun Ju Sung, Angie S. Wenzlaff, Chen Wu, Dankyu Yoon, Ying Ting Chen, Yu Ching ChengYoon Shin Cho, Sean P. David, Jubao Duan, Charles B. Eaton, Helena Furberg, Alison M. Goate, Dongfeng Gu, Helen M. Hansen, Sarah Hartz, Zhibin Hu, Young Jin Kim, Steven J. Kittner, Douglas F. Levinson, Thomas H. Mosley, Thomas J. Payne, D. C. Rao, John P. Rice, Treva K. Rice, Tae Hwi Schwantes-An, Sanjay S. Shete, Jianxin Shi, Margaret R. Spitz, Yan V. Sun, Fuu Jen Tsai, Jen C. Wang, Margaret R. Wrensch, Hong Xian, Pablo V. Gejman, Jiang He, Steven Hunt, Sharon L. Kardia, Ming D. Li, Dongxin Lin, Braxton D. Mitchell, Taesung Park, Ann G. Schwartz, Hongbing Shen, John K. Wiencke, Jer Yuarn Wu, Jun Yokota, Christopher I. Amos, Laura J. Bierut

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 languageEnglish
Pages (from-to)340-351
Number of pages12
JournalGenetic Epidemiology
Volume36
Issue number4
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Fingerprint

Asian Americans
African Americans
Meta-Analysis
Chromosomes
Smoking
Population
Genetic Markers
Tobacco Products
Odds Ratio
Phenotype

Keywords

  • Cross-population
  • Genetics
  • Meta-analysis
  • Smoking

ASJC Scopus subject areas

  • Epidemiology
  • Medicine(all)
  • Genetics(clinical)

Cite this

Chen, L. S., Saccone, N. L., Culverhouse, R. C., Bracci, P. M., Chen, C. H., Dueker, N., ... Bierut, L. J. (2012). Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25. Genetic Epidemiology, 36(4), 340-351. https://doi.org/10.1002/gepi.21627

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 journalArticle

Chen, LS, Saccone, NL, Culverhouse, RC, Bracci, PM, Chen, CH, Dueker, N, Han, Y, Huang, H, Jin, G, Kohno, T, Ma, JZ, Przybeck, TR, Sanders, AR, Smith, JA, Sung, YJ, Wenzlaff, AS, Wu, C, Yoon, D, Chen, YT, Cheng, YC, Cho, YS, David, SP, Duan, J, Eaton, CB, Furberg, H, Goate, AM, Gu, D, Hansen, HM, Hartz, S, Hu, Z, Kim, YJ, Kittner, SJ, Levinson, DF, Mosley, TH, Payne, TJ, Rao, DC, Rice, JP, Rice, TK, Schwantes-An, TH, Shete, SS, Shi, J, Spitz, MR, Sun, YV, Tsai, FJ, Wang, JC, Wrensch, MR, Xian, H, Gejman, PV, He, J, Hunt, S, Kardia, SL, Li, MD, Lin, D, Mitchell, BD, Park, T, Schwartz, AG, Shen, H, Wiencke, JK, Wu, JY, Yokota, J, Amos, CI & Bierut, LJ 2012, 'Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25', Genetic Epidemiology, vol. 36, no. 4, pp. 340-351. https://doi.org/10.1002/gepi.21627
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. / Smoking and genetic risk variation across populations of European, Asian, and African American ancestry-a meta-analysis of chromosome 15q25. In: Genetic Epidemiology. 2012 ; Vol. 36, No. 4. pp. 340-351.
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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.",
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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.

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KW - Cross-population

KW - Genetics

KW - Meta-analysis

KW - Smoking

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