Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.
- Authors
- 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 C; 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
- Year
- 2012
- Journal
- Genetic epidemiology
- PMID
- 22539395
- DOI
- 10.1002/gepi.21627
- PMCID
- PMC3387741
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.
Top associations with heavy vs. light smoking: Bin A across three populationsFigure 1 shows all 52 SNPs in bin A, and also the only consistently associated sub-bins (p<0.01 in both Asians and African Americans). This figure also lists corresponding odds ratios for the association between the sub-bins and heavy smoking. bin A variants span across six genes in the European ancestry population, the sub-bin tagged by rs16969968 in the Asian population spans across two genes, and the sub-bin tagged by rs16969968 in the African American population spans across only one gene (CHRNA5).
LLM interpretation
This figure consists of a genomic map and three associated data tables comparing SNP associations with heavy smoking across European, Asian, and African American ancestries. The top diagram maps 52 SNPs in "bin A" across six genes (including *CHRNA5*), with blue triangles indicating specific variants. The tables list the tag SNP (rs16969968), odds ratios (ranging from 1.31 to 1.64), and p-values (all < 0.01), alongside the specific genomic spans included in each population's locus or sub-locus.
Rs16969968 and heavy smoking in samples of European, Asian, and African American ancestryThe ORs and 95% CIs are for the effect per allele using additive coding in the logistic regression with age and sex as covariates. *When rs16969968 is not available, rs1051730 and rs951266 are used as proxy SNPs in European and Asian ancestry samples.
LLM interpretation
This figure consists of three forest plots showing the association between the SNP rs16969968 and heavy smoking across European, Asian, and African American ancestry groups. Each plot displays odds ratios (OR) and 95% confidence intervals (CI) for individual studies, with a summary diamond representing the pooled effect. All three ancestry groups show a statistically significant positive association, with summary ORs of 1.31 (p=1.3e-14), 1.64 (p=0.0058), and 1.62 (p=0.0011), respectively.
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