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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).

TitleGenome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Publication TypePublication
AuthorsSaccone NL, Emery LS, Sofer T, Gogarten SM, Becker DM, Bottinger EP, Chen L-S, Culverhouse RC, Duan W, Hancock DB, H Hosgood D, Johnson EO, Loos RJF, Louie T, Papanicolaou G, Perreira KM, Rodriquez EJ, Schurmann C, Stilp AM, Szpiro AA, Talavera GA, Taylor KD, Thrasher JF, Yanek LR, Laurie CC, Pérez-Stable EJ, Bierut LJ, Kaplan RC
JournalNicotine Tob Res
Date Published2018 Mar 06
KeywordsAdult, Female, Gene Frequency, genome-wide association study, Genotype, Hispanic or Latino, Humans, Male, Middle Aged, Nerve Tissue Proteins, Public Health, Receptors, Nicotinic, Smoking, United States

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.

Alternate JournalNicotine Tob Res
PubMed ID28520984
PubMed Central IDPMC5896462
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
R01 DA035825 / DA / NIDA NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Affiliated Investigator - Not at HCHS/SOL site
Manuscript Status: