Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Rachel M Freathy; Gbenga R Kazeem; Richard W Morris; Paul C D Johnson; Lavinia Paternoster; Shah Ebrahim; Andrew T Hattersley; Anita Hill; Aroon D Hingorani; Claus Holst; Barbara J Jefferis; Sofia I I Kring; Vincent Mooser; Sandosh Padmanabhan; Martin Preisig; Susan M Ring; Naveed Sattar; Mark N Upton; Peter Vollenweider; Gerard Waeber; Thorkild I A Sørensen; Timothy M Frayling; Graham Watt; Debbie A Lawlor; Peter H Whincup; Federica Tozzi; George Davey Smith; Marcus Munafò

doi:10.1093/ije/dyr077

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Rachel M Freathy, Gbenga R Kazeem, Richard W Morris, Paul C D Johnson, Lavinia Paternoster, Shah Ebrahim, Andrew T Hattersley, Anita Hill, Aroon D Hingorani, Claus Holst, Barbara J Jefferis, Sofia I I Kring, Vincent Mooser, Sandosh Padmanabhan, Martin Preisig, Susan M Ring, Naveed Sattar, Mark N Upton, Peter Vollenweider, Gerard WaeberThorkild I A Sørensen, Timothy M Frayling, Graham Watt, Debbie A Lawlor, Peter H Whincup, Federica Tozzi, George Davey Smith, Marcus Munafò

79 Citationer (Scopus)

Abstract

Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction.Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m² [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m² (95% CI: 0.13-0.31) lower BMI (P = 8 × 10^-6). The effect size was larger in current [0.33 kg/m² lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10^-5], than in former smokers [0.16 kg/m² (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001).Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI. Published by Oxford University Press on behalf of the International Epidemiological Association

Originalsprog	Engelsk
Tidsskrift	International Journal of Epidemiology
Vol/bind	40
Udgave nummer	6
Sider (fra-til)	1617-28
Antal sider	12
ISSN	0300-5771
DOI	https://doi.org/10.1093/ije/dyr077 https://doi.org/10.1093/ije/dyr077
Status	Udgivet - 1 dec. 2011

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Freathy, R. M., Kazeem, G. R., Morris, R. W., Johnson, P. C. D., Paternoster, L., Ebrahim, S., Hattersley, A. T., Hill, A., Hingorani, A. D., Holst, C., Jefferis, B. J., Kring, S. I. I., Mooser, V., Padmanabhan, S., Preisig, M., Ring, S. M., Sattar, N., Upton, M. N., Vollenweider, P., ... Munafò, M. (2011). Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index. International Journal of Epidemiology, 40(6), 1617-28. https://doi.org/10.1093/ije/dyr077, https://doi.org/10.1093/ije/dyr077

Freathy, RM, Kazeem, GR, Morris, RW, Johnson, PCD, Paternoster, L, Ebrahim, S, Hattersley, AT, Hill, A, Hingorani, AD, Holst, C, Jefferis, BJ, Kring, SII, Mooser, V, Padmanabhan, S, Preisig, M, Ring, SM, Sattar, N, Upton, MN, Vollenweider, P, Waeber, G, Sørensen, TIA, Frayling, TM, Watt, G, Lawlor, DA, Whincup, PH, Tozzi, F, Davey Smith, G & Munafò, M 2011, 'Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index', International Journal of Epidemiology, bind 40, nr. 6, s. 1617-28. https://doi.org/10.1093/ije/dyr077, https://doi.org/10.1093/ije/dyr077

@article{c572e8dce831449f91066de67a450289,

title = "Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index",

abstract = "Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction.Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m2 [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m2 (95% CI: 0.13-0.31) lower BMI (P = 8 × 10-6). The effect size was larger in current [0.33 kg/m2 lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10-5], than in former smokers [0.16 kg/m2 (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001).Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI. Published by Oxford University Press on behalf of the International Epidemiological Association",

author = "Freathy, {Rachel M} and Kazeem, {Gbenga R} and Morris, {Richard W} and Johnson, {Paul C D} and Lavinia Paternoster and Shah Ebrahim and Hattersley, {Andrew T} and Anita Hill and Hingorani, {Aroon D} and Claus Holst and Jefferis, {Barbara J} and Kring, {Sofia I I} and Vincent Mooser and Sandosh Padmanabhan and Martin Preisig and Ring, {Susan M} and Naveed Sattar and Upton, {Mark N} and Peter Vollenweider and Gerard Waeber and S{\o}rensen, {Thorkild I A} and Frayling, {Timothy M} and Graham Watt and Lawlor, {Debbie A} and Whincup, {Peter H} and Federica Tozzi and {Davey Smith}, George and Marcus Munaf{\`o}",

year = "2011",

month = dec,

day = "1",

doi = "10.1093/ije/dyr077",

language = "English",

volume = "40",

pages = "1617--28",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

AU - Freathy, Rachel M

AU - Kazeem, Gbenga R

AU - Morris, Richard W

AU - Johnson, Paul C D

AU - Paternoster, Lavinia

AU - Ebrahim, Shah

AU - Hattersley, Andrew T

AU - Hill, Anita

AU - Hingorani, Aroon D

AU - Holst, Claus

AU - Jefferis, Barbara J

AU - Kring, Sofia I I

AU - Mooser, Vincent

AU - Padmanabhan, Sandosh

AU - Preisig, Martin

AU - Ring, Susan M

AU - Sattar, Naveed

AU - Upton, Mark N

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Sørensen, Thorkild I A

AU - Frayling, Timothy M

AU - Watt, Graham

AU - Lawlor, Debbie A

AU - Whincup, Peter H

AU - Tozzi, Federica

AU - Davey Smith, George

AU - Munafò, Marcus

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction.Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m2 [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m2 (95% CI: 0.13-0.31) lower BMI (P = 8 × 10-6). The effect size was larger in current [0.33 kg/m2 lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10-5], than in former smokers [0.16 kg/m2 (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001).Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI. Published by Oxford University Press on behalf of the International Epidemiological Association

AB - Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction.Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m2 [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m2 (95% CI: 0.13-0.31) lower BMI (P = 8 × 10-6). The effect size was larger in current [0.33 kg/m2 lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10-5], than in former smokers [0.16 kg/m2 (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001).Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI. Published by Oxford University Press on behalf of the International Epidemiological Association

U2 - 10.1093/ije/dyr077

DO - 10.1093/ije/dyr077

M3 - Journal article

C2 - 21593077

SN - 0300-5771

VL - 40

SP - 1617

EP - 1628

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 6

ER -

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

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