Genome-Wide Association Study of Heavy Smoking and Daily/Nondaily Smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Authors

Saccone, Nancy L; Emery, Leslie S; Sofer, Tamar; Gogarten, Stephanie M; Becker, Diane M; Bottinger, Erwin P; Chen, Li-Shiun; Culverhouse, Robert C; Duan, Weimin; Hancock, Dana B; Hosgood, H Dean; Johnson, Eric O; Loos, Ruth J F; Louie, Tin; Papanicolaou, George; Perreira, Krista M; Rodriquez, Erik J; Schurmann, Claudia; Stilp, Adrienne M; Szpiro, Adam A; Talavera, Gregory A; Taylor, Kent D; Thrasher, James F; Yanek, Lisa R; Laurie, Cathy C; Pérez-Stable, Eliseo J; Bierut, Laura J; Kaplan, Robert C

Year

2018

Journal

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

PMID

28520984

DOI

10.1093/ntr/ntx107

PMCID

PMC5896462

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.

No figures extracted from this document.

No chunks — full text not yet ingested.

No entities extracted from this document yet.

No uploaded files.

No citations found.

In this knowledge base

External