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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)
Saccone, N. L., Emery, L. S., Sofer, T., Gogarten, S. M., Becker, D. M., Bottinger, E. P., Chen, L.-S., Culverhouse, R. C., Duan, W., Hancock, D. B., Hosgood, H. D., Johnson, E. O., Loos, R. J. F., Louie, T., Papanicolaou, G., Perreira, K. M., Rodriquez, E. J., Schurmann, C., Stilp, A. M., ... Kaplan, R. C. (2018). Genome-wide association study of heavy smoking and daily/nondaily smoking in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Nicotine and Tobacco Research, 20(4), 448-457. https://doi.org/10.1093/ntr/ntx107
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 similar to 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 alpha 5 cholinergic nicotinic receptor subunit, was associated with heavy smoking at genome-wide significance (p <= 5 x 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 x 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.
