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 R.
AU - Laurie, Cathy C.
AU - Pérez-Stable, Eliseo J.
AU - Bierut, Laura J.
AU - Kaplan, Robert C.
N1 - Funding Information:
The baseline examination of the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000124, and NIDDK Diabetes Research Center (DRC) grant DK063491. The Mount Sinai BioMe Biobank is supported by The Andrea and Charles Bronfman Philanthropies and genotyping has been in part supported by a grant from NHGRI (HG007417). COGEND is supported by P01CA89392 from the National Cancer Institute; COGEND genotyping was funded by 1 X01 HG005274-01 and performed at Center for Inherited Disease Research (CIDR) which is funded through a federal contract from NIH to JHU (HHSN268200782096C). GeneSTAR was supported by grants (U01 HL72518 and HL087698) from the National Institutes of Health/National Heart, Lung, and Blood Institute and by a grant from the National Institutes of Health/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. We would like to acknowledge the following additional funding support. From the National Institute on Drug Abuse (NIDA): R01 DA026911; R01 DA036583; R01DA035825; R01 DA019963; R01 DA013423; R21 DA038241. From the National Institute on Aging: P30 AG15272. This research was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. We thank the participants and staff of the HCHS/SOL study for their contributions to this study. This manuscript has been reviewed by the HCHS/ SOL Publications Committee for scientific content and consistency of data interpretation with previous HCHS/SOL publications. We thank Erin Rice for administrative and communications support. Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the views or the official position(s) of the National Institutes of Health or any of the sponsoring organizations and agencies of the US government.
Funding Information:
The baseline examination of the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The Genetic Analysis Center at the University of Washington was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Genotyping efforts were supported by NHLBI HSN 26220/20054C, NCATS CTSI grant UL1TR000124, and NIDDK Diabetes Research Center (DRC) grant DK063491. The Mount Sinai BioMe Biobank is supported by The Andrea and Charles Bronfman Philanthropies and genotyping has been in part supported by a grant from NHGRI (HG007417). COGEND is supported by P01CA89392 from the National Cancer Institute; COGEND genotyping was funded by 1 X01 HG005274-01 and performed at Center for Inherited Disease Research (CIDR) which is funded through a federal contract from NIH to JHU (HHSN268200782096C). GeneSTAR was supported by grants (U01 HL72518 and HL087698) from the National Institutes of Health/National Heart, Lung, and Blood Institute and by a grant from the National Institutes of Health/National Center for Research Resources (M01-RR000052) to the Johns Hopkins General Clinical Research Center. We would like to acknowledge the following additional funding support. From the National Institute on Drug Abuse (NIDA): R01 DA026911; R01 DA036583; R01DA035825; R01 DA019963; R01 DA013423; R21 DA038241. From the National Institute on Aging: P30 AG15272. This research was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health.
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.
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
M3 - Article
C2 - 28520984
AN - SCOPUS:85042876839
SN - 1462-2203
VL - 20
SP - 448
EP - 457
JO - Nicotine and Tobacco Research
JF - Nicotine and Tobacco Research
IS - 4
ER -