Genome-wide meta-analyses of smoking behaviors in African Americans.
paper
Cited
Public
- Authors
- David, S P; Hamidovic, A; Chen, G K; Bergen, A W; Wessel, J; Kasberger, J L; Brown, W M; Petruzella, S; Thacker, E L; Kim, Y; Nalls, M A; Tranah, G J; Sung, Y J; Ambrosone, C B; Arnett, D; Bandera, E V; Becker, D M; Becker, L; Berndt, S I; Bernstein, L; Blot, W J; Broeckel, U; Buxbaum, S G; Caporaso, N; Casey, G; Chanock, S J; Deming, S L; Diver, W R; Eaton, C B; Evans, D S; Evans, M K; Fornage, M; Franceschini, N; Harris, T B; Henderson, B E; Hernandez, D G; Hitsman, B; Hu, J J; Hunt, S C; Ingles, S A; John, E M; Kittles, R; Kolb, S; Kolonel, L N; Le Marchand, L; Liu, Y; Lohman, K K; McKnight, B; Millikan, R C; Murphy, A; Neslund-Dudas, C; Nyante, S; Press, M; Psaty, B M; Rao, D C; Redline, S; Rodriguez-Gil, J L; Rybicki, B A; Signorello, L B; Singleton, A B; Smoller, J; Snively, B; Spring, B; Stanford, J L; Strom, S S; Swan, G E; Taylor, K D; Thun, M J; Wilson, A F; Witte, J S; Yamamura, Y; Yanek, L R; Yu, K; Zheng, W; Ziegler, R G; Zonderman, A B; Jorgenson, E; Haiman, C A; Furberg, H
- Year
- 2012
- Journal
- Translational psychiatry
- PMID
- 22832964
- DOI
- 10.1038/tp.2012.41
- PMCID
- PMC3365260
The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (Ξ² = 0.040, s.e. = 0.007, P = 1.84 Γ 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.
Double genomic control (GC)-corrected Manhattan plots showing significance of association of all single-nucleotide polymorphisms (SNPs) for four smoking phenotypes. (aβd). SNPs plotted on the x axis according to their position on each chromosome against, on the y axis (shown as βlog10 P-value), the association with (a) smoking initiation (SI, ever vs never smokers), (b) age of SI, (c) cigarettes smoked per day, and (d) smoking cessation (former vs current smokers). Dotted red line indicates genome-wide significance threshold of P<5 Γ 10β8.
LLM interpretation
This figure consists of four Manhattan plots (aβd) showing the association of SNPs across chromosomes (x-axis) with four smoking phenotypes: smoking initiation, age of initiation, cigarettes smoked per day, and smoking cessation. The y-axis represents the $-\log_{10} P\text{-value}$, with a dotted red line indicating the genome-wide significance threshold of $P < 5 \times 10^{-8}$. In all four plots, the data points remain below the red significance threshold, indicating no SNPs reached genome-wide significance for these phenotypes.
Forest and regional plot of rs2036527 with cigarettes smoked per day (CPD) from meta-analyses of the Study of Tobacco in Minority Populations (STOMP) consortia. Forest plot showing effect sizes across studies; I2=41.6%. Regional association plot show single-nucleotide polymorphisms (SNPs) plotted by position on chromosome against βlog10 P-value. Estimated recombination rates (from HapMap-CEU) are plotted in light blue to reflect the local linkage disequilibrium (LD) structure on a secondary y axis. The SNPs surrounding the most significant SNP (purple) are color-coded to reflect their LD with this SNP (using pairwise r2 values from HapMap-CEU): orange, r20.8, red; 0.6β0.8, orange; 0.6β0.8; green, 0.4β0.6, light blue, 0.2β0.4; dark blue, <0.2. The blue bars at the bottom of the plot represent the relative size and location of genes in the region. AABC, African American GWAS consortia of Breast cancer; AAPC, African American GWAS consortia of Prostate Cancer; ARIC, Atherosclerosis Risk in Communities; CARDIA, Coronary Artery Risk Development in Young Adults; CFS, Cleveland Family Study; JHS, Jackson Heart Study; MESA, Multi-Ethnic Study of Atherosclerosis; HANDLS, Healthy Aging in Neighborhoods across the Life Span Study; HYPGEN, Hypertension Genetic Epidemiology Network; WHI, Women's Health Initiative.
LLM interpretation
This figure consists of a forest plot and a regional association plot analyzing the SNP rs2036527 in relation to cigarettes smoked per day (CPD). The forest plot displays positive beta effect sizes across multiple study cohorts (e.g., AABC, WHI), with a summary diamond indicating an overall positive effect and an $I^2$ of 41.6%. The regional plot shows $-\log_{10} P$-values for SNPs on chromosome 15, with rs2036527 as the most significant (purple), color-coded by linkage disequilibrium ($r^2$) and overlaid with recombination rates and gene locations (e.g., *CHRNA5*, *CHRNA3*).
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In this knowledge base
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