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Chunk #12 — Results

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Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs.
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In comparing data from successful vs unsuccessful quitters, we identified 4,570 SNPs whose allele frequencies differ between these two groups with t values for these differences that yield nominal p values < 0.01. The nominally-positive SNPs from comparisons between successful vs unsuccessful quitters cluster together to extents much greater than expected by chance if their allelic frequencies were independent of each other (Monte Carlo p < 0.00001). 944 of the 4,570 nominally-positive SNPs lay in 224 clusters in which each positive SNP lay within 100 Kb of at least one other positive SNP. We would anticipate such clustering if many of these reproducibly-positive SNPs identified haplotypes that were present in different frequencies in our samples of successful vs unsuccessful quitters, but not if they represented chance independent observations. We defined clusters as chromosomal sites where 1) three or more reproducibly-positive SNPs were positioned within 0.1 Mb of each other and 2) reproducibly-positive SNPs assessed by two different array types were represented, so that all positive data did not come from just Nsp I or from Sty I arrays.