• Article

Genome-wide association study of heavy smoking and daily/nondaily smoking in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

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 U.S. 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, 5,119 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 1,929 ever smokers reporting cigarettes-per-day (CPD) > 10 versus 3,156 reporting CPD ≤ 10. The functional variant rs16969968 in CHRNA5 had a p-value of 2.20×10-7 and odds ratio 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.

Citation

Saccone, N. L., Emery, L. S., Sofer, T., Gogarten, S. M., Becker, D. M., Bottinger, E. P., ... 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. DOI: 10.1093/ntr/ntx107

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