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Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans

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Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans. / Chenoweth, M.J.; Cox, L.S.; Nollen, N.L.; Ahluwalia, J.S.; Benowitz, N.L.; Lerman, C.; Knight, J.; Tyndale, R.F.

In: Scientific Reports, Vol. 11, No. 1, 19572, 01.10.2021.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Chenoweth, MJ, Cox, LS, Nollen, NL, Ahluwalia, JS, Benowitz, NL, Lerman, C, Knight, J & Tyndale, RF 2021, 'Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans', Scientific Reports, vol. 11, no. 1, 19572. https://doi.org/10.1038/s41598-021-98883-z

APA

Chenoweth, M. J., Cox, L. S., Nollen, N. L., Ahluwalia, J. S., Benowitz, N. L., Lerman, C., Knight, J., & Tyndale, R. F. (2021). Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans. Scientific Reports, 11(1), [19572]. https://doi.org/10.1038/s41598-021-98883-z

Vancouver

Chenoweth MJ, Cox LS, Nollen NL, Ahluwalia JS, Benowitz NL, Lerman C et al. Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans. Scientific Reports. 2021 Oct 1;11(1). 19572. https://doi.org/10.1038/s41598-021-98883-z

Author

Chenoweth, M.J. ; Cox, L.S. ; Nollen, N.L. ; Ahluwalia, J.S. ; Benowitz, N.L. ; Lerman, C. ; Knight, J. ; Tyndale, R.F. / Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans. In: Scientific Reports. 2021 ; Vol. 11, No. 1.

Bibtex

@article{ce4100c29e594c47a0f70fd0330fc5de,
title = "Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans",
abstract = "Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.",
author = "M.J. Chenoweth and L.S. Cox and N.L. Nollen and J.S. Ahluwalia and N.L. Benowitz and C. Lerman and J. Knight and R.F. Tyndale",
year = "2021",
month = oct,
day = "1",
doi = "10.1038/s41598-021-98883-z",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans

AU - Chenoweth, M.J.

AU - Cox, L.S.

AU - Nollen, N.L.

AU - Ahluwalia, J.S.

AU - Benowitz, N.L.

AU - Lerman, C.

AU - Knight, J.

AU - Tyndale, R.F.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.

AB - Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.

U2 - 10.1038/s41598-021-98883-z

DO - 10.1038/s41598-021-98883-z

M3 - Journal article

VL - 11

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 19572

ER -