Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Oxford University Press, 2017
Online
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INTRODUCTION: Genetic variants associated with nicotine dependence have previously been identified, primarily in European-ancestry populations. No genome-wide association studies (GWAS) have been reported for smoking behaviors in Hispanics/Latinos in the United States and Latin America, who are of mixed ancestry with European, African, and American Indigenous components. METHODS: We examined genetic associations with smoking behaviors in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (N = 12 741 with smoking data, 5119 ever-smokers), using ~2.3 million genotyped variants imputed to the 1000 Genomes Project phase 3. Mixed logistic regression models accounted for population structure, sampling, relatedness, sex, and age. RESULTS: The known region of CHRNA5, which encodes the α5 cholinergic nicotinic receptor subunit, was associated with heavy smoking at genome-wide significance (p ≤ 5 × 10(–8)) in a comparison of 1929 ever-smokers reporting cigarettes per day (CPD) > 10 versus 3156 reporting CPD ≤ 10. The functional variant rs16969968 in CHRNA5 had a p value of 2.20 × 10(–7) and odds ratio (OR) of 1.32 for the minor allele (A); its minor allele frequency was 0.22 overall and similar across Hispanic/Latino background groups (Central American = 0.17; South American = 0.19; Mexican = 0.18; Puerto Rican = 0.22; Cuban = 0.29; Dominican = 0.19). CHRNA4 on chromosome 20 attained p < 10(–4), supporting prior findings in non-Hispanics. For nondaily smoking, which is prevalent in Hispanic/Latino smokers, compared to daily smoking, loci on chromosomes 2 and 4 achieved genome-wide significance; replication attempts were limited by small Hispanic/Latino sample sizes. CONCLUSIONS: Associations of nicotinic receptor gene variants with smoking, first reported in non-Hispanic European-ancestry populations, generalized to Hispanics/Latinos despite different patterns of smoking behavior. IMPLICATIONS: We conducted the first large-scale genome-wide association study (GWAS) of smoking behavior in a US Hispanic/Latino cohort, and the first GWAS of daily/nondaily smoking in any population. Results show that the region of the nicotinic receptor subunit gene CHRNA5, which in non-Hispanic European-ancestry smokers has been associated with heavy smoking as well as cessation and treatment efficacy, is also significantly associated with heavy smoking in this Hispanic/Latino cohort. The results are an important addition to understanding the impact of genetic variants in understudied Hispanic/Latino smokers.
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Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
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Autor/in / Beteiligte Person: | Duan, Weimin ; Bottinger, Erwin P. ; Hancock, Dana B. ; Szpiro, Adam A. ; Louie, Tin ; Saccone, Nancy L. ; Johnson, Eric O. ; Talavera, Gregory A. ; Perreira, Krista M. ; Kaplan, Robert C. ; Emery, Leslie S. ; Yanek, Lisa R. ; Sofer, Tamar ; Bierut, Laura J. ; Stilp, Adrienne M. ; Loos, Ruth J. F. ; Schurmann, Claudia ; Culverhouse, Robert ; H. Dean Hosgood ; Laurie, Cathy C. ; Chen, Li-Shiun ; Papanicolaou, George ; Thrasher, James F. ; Taylor, Kent D. ; Rodriquez, Erik J. ; Becker, Diane M. ; Pérez-Stable, Eliseo J. ; Gogarten, Stephanie M. |
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Veröffentlichung: | Oxford University Press, 2017 |
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