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

Nancy L. Saccone, Leslie S. Emery, Tamar Sofer, Stephanie M. Gogarten, Diane M Becker, Erwin P. Bottinger, Li Shiun Chen, Robert C. Culverhouse, Weimin Duan, Dana B. Hancock, H. Dean Hosgood, Eric O. Johnson, Ruth J.F. Loos, Tin Louie, George Papanicolaou, Krista M. Perreira, Erik J. Rodriquez, Claudia Schurmann, Adrienne M. Stilp, Adam A. Szpiro & 8 others Gregory A. Talavera, Kent D. Taylor, James F. Thrasher, Lisa Yanek, Cathy C. Laurie, Eliseo J. Pérez-Stable, Laura J. Bierut, Robert C. Kaplan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)448-457
Number of pages10
JournalNicotine and Tobacco Research
Volume20
Issue number4
DOIs
StatePublished - Mar 6 2018

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Genome-Wide Association Study
Hispanic Americans
Smoking
Health
Nicotinic Receptors
Genome
Tobacco Products
Population
Logistic Models
Chromosomes, Human, Pair 20
Tobacco Use Disorder
Chromosomes, Human, Pair 4
Withholding Treatment
Chromosomes, Human, Pair 2
Latin America

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

Cite this

Genome-wide association study of heavy smoking and daily/nondaily smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). / 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; Laurie, Cathy C.; Pérez-Stable, Eliseo J.; Bierut, Laura J.; Kaplan, Robert C.

In: Nicotine and Tobacco Research, Vol. 20, No. 4, 06.03.2018, p. 448-457.

Research output: Contribution to journalArticle

Saccone, NL, Emery, LS, Sofer, T, Gogarten, SM, Becker, DM, Bottinger, EP, Chen, LS, Culverhouse, RC, Duan, W, Hancock, DB, Hosgood, HD, 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, L, Laurie, CC, Pérez-Stable, EJ, Bierut, LJ & Kaplan, RC 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, vol. 20, no. 4, pp. 448-457. https://doi.org/10.1093/ntr/ntx107
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 ; Laurie, Cathy C. ; Pérez-Stable, Eliseo J. ; Bierut, Laura J. ; Kaplan, Robert C. / Genome-wide association study of heavy smoking and daily/nondaily smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In: Nicotine and Tobacco Research. 2018 ; Vol. 20, No. 4. pp. 448-457.
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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.",
author = "Saccone, {Nancy L.} and Emery, {Leslie S.} and Tamar Sofer and Gogarten, {Stephanie M.} and Becker, {Diane M} and Bottinger, {Erwin P.} and Chen, {Li Shiun} and Culverhouse, {Robert C.} and Weimin Duan and Hancock, {Dana B.} and Hosgood, {H. Dean} and Johnson, {Eric O.} and Loos, {Ruth J.F.} and Tin Louie and George Papanicolaou and Perreira, {Krista M.} and Rodriquez, {Erik J.} and Claudia Schurmann and Stilp, {Adrienne M.} and Szpiro, {Adam A.} and Talavera, {Gregory A.} and Taylor, {Kent D.} and Thrasher, {James F.} and Lisa Yanek and Laurie, {Cathy C.} and P{\'e}rez-Stable, {Eliseo J.} and Bierut, {Laura J.} and Kaplan, {Robert C.}",
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TY - JOUR

T1 - Genome-wide association study of heavy smoking and daily/nondaily smoking in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

AU - Saccone, Nancy L.

AU - Emery, Leslie S.

AU - Sofer, Tamar

AU - Gogarten, Stephanie M.

AU - Becker, Diane M

AU - Bottinger, Erwin P.

AU - Chen, Li Shiun

AU - Culverhouse, Robert C.

AU - Duan, Weimin

AU - Hancock, Dana B.

AU - Hosgood, H. Dean

AU - Johnson, Eric O.

AU - Loos, Ruth J.F.

AU - Louie, Tin

AU - Papanicolaou, George

AU - Perreira, Krista M.

AU - Rodriquez, Erik J.

AU - Schurmann, Claudia

AU - Stilp, Adrienne M.

AU - Szpiro, Adam A.

AU - Talavera, Gregory A.

AU - Taylor, Kent D.

AU - Thrasher, James F.

AU - Yanek, Lisa

AU - Laurie, Cathy C.

AU - Pérez-Stable, Eliseo J.

AU - Bierut, Laura J.

AU - Kaplan, Robert C.

PY - 2018/3/6

Y1 - 2018/3/6

N2 - 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.

AB - 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.

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U2 - 10.1093/ntr/ntx107

DO - 10.1093/ntr/ntx107

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JO - Nicotine and Tobacco Research

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SN - 1462-2203

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