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Nicotine Tob Res. 2018 Mar 6;20(4):448-457. doi: 10.1093/ntr/ntx107.

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

Author information

1
Department of Genetics, Washington University School of Medicine, St. Louis, MO.
2
Department of Biostatistics, University of Washington, Seattle, WA.
3
GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
4
Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
5
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
6
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
7
Behavioral and Urban Health Program, Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC.
8
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
9
Fellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, NC.
10
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
11
Department of Public Policy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
12
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
13
Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA.
14
Graduate School of Public Health, San Diego State University, San Diego, CA.
15
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.
16
Department of Health Promotion, Education and Behavior, University of South Carolina, Columbia, SC.
17
National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD.

Abstract

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.

PMID:
28520984
PMCID:
PMC5896462
DOI:
10.1093/ntr/ntx107
[Indexed for MEDLINE]
Free PMC Article

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