Hemizygous Deletion on Chromosome 3p26.1 Is Associated with Heavy Smoking among African American Subjects in the COPDGene Study.
paper
Cited
Public
- Authors
- Begum, Ferdouse; Ruczinski, Ingo; Hokanson, John E; Lutz, Sharon M; Parker, Margaret M; Cho, Michael H; Hetmanski, Jacqueline B; Scharpf, Robert B; Crapo, James D; Silverman, Edwin K; Beaty, Terri H
- Year
- 2016
- Journal
- PloS one
- PMID
- 27711239
- DOI
- 10.1371/journal.pone.0164134
- PMCID
- PMC5053531
Many well-powered genome-wide association studies have identified genetic determinants of self-reported smoking behaviors and measures of nicotine dependence, but most have not considered the role of structural variants, such as copy number variation (CNVs), influencing these phenotypes. Here, we included 2,889 African American and 6,187 non-Hispanic White subjects from the COPDGene cohort (http://www.copdgene.org) to carefully investigate the role of polymorphic CNVs across the genome on various measures of smoking behavior. We identified a CNV component (a hemizygous deletion) on chromosome 3p26.1 associated with two quantitative phenotypes related to smoking behavior among African Americans. This polymorphic hemizygous deletion is significantly associated with pack-years and cigarettes smoked per day among African American subjects in the COPDGene study. We sought evidence of replication in African Americans from the population based Atherosclerosis Risk in Communities (ARIC) study. While we observed similar CNV counts, the extent of exposure to cigarette smoking among ARIC subjects was quite different and the smaller sample size of heavy smokers in ARIC severely limited statistical power, so we were unable to replicate our findings from the COPDGene cohort. But meta-analyses of COPDGene and ARIC study subjects strengthened our association signal. However, a few linkage studies have reported suggestive linkage to the 3p26.1 region, and a few genome-wide association studies (GWAS) have reported markers in the gene (GRM7) nearest to this 3p26.1 area of polymorphic deletions are associated with measures of nicotine dependence among subjects of European ancestry.
Genome-wide CNV association scan for pack-years in African American COPDGene subjects: Each point represents a CNV component estimated by PennCNV.The red dotted line at 3.5 represents the genome-wide significance levels needed to maintain a family-wise error rate (FWER) of 5%, obtained via 10,000 permutation tests. The black dotted line at 3.87 represents the genome-wide significance levels for Bonferroni correction. 22 vertical bands indicate the 22 autosomes examined.
Mean and 95% Confidence Interval (CI) plot of pack-years for two groups of AA subjects.a. Mean pack-years and 95%CI in 77 hemizygous deletion carriers vs. rest of the subjects(2812) in chr 3p26.1. The observed mean difference in pack-years was statistically significantly (p = 0.00629) between these two groups.
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In this knowledge base
| Title | Year | PMID |
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| Human Genetics of Addiction: New Insights and Future Directions. | 2018 | 29504045 |
| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients. | Zaki-Dizaji M et al. | — | 2024 | → |
| Genetic Advances in Chronic Obstructive Pulmonary Disease. Insights from COPDGene. | Ragland MF et al. | — | 2019 | → |
| Human Genetics of Addiction: New Insights and Future Directions. | Hancock DB et al. | — | 2018 | → |
| Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. | Ji X et al. | — | 2018 | → |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | — | 2017 | → |