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Chunk #10 — Results — Polymorphic CNV Association Analysis of Pack-years of Smoking in AA Subjects

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Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study.
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Considering only polymorphic CNV components (i.e. those with >1% frequency among AA subjects), there were genome-wide 373 CNV components encompassing 22 autosomes available for association testing among all 2,889 AA subjects. We adjusted for age, gender and admixture scores (i.e., the estimated average European ancestry among AA subjects) in testing for association with pack-years of smoking. Fig 1 shows the Manhattan plot of 373 polymorphic CNV components, and its corresponding QQ plot is presented in S3 Fig. After multiple comparison adjustment, only one polymorphic CNV component on chromosome 3p26.1 (spanning 1,691 bp from position 6212573 to 6214264, hg18) showed genome-wide significance (p = 0.00017; -log10(0.00017)~3.77) (S4 Fig). The raw intensity data (LRRs and BAFs) at chr3p26.1 were of high quality, and all CNV calls were made with high confidence (see S5 Fig). Fig 2 shows the mean pack-years and 95% confidence interval (CI) plots for different polymorphic CNV counts between 77 hemizygous deletion carriers and the remaining AA subjects for this region of chr 3p26.1. Mean pack-years was statistically significantly different (p = 0.00629) between 77 hemizygous deletion carriers and rest of the AA individuals.