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.