A common biological basis of obesity and nicotine addiction.

T E Thorgeirsson,Engage Consortium ,Oxford-Gsk Consortium ,J Marchini,P Sulem,G B Walters,D F Gudbjartsson,M I Mccarthy,K Stefansson,P F Sullivan,H Furberg,U Styrkarsdottir,V Steinthorsdottir,S Besenbacher,Tag Consortium ,U Thorsteinsdottir,G Thorleifsson

doi:10.1038/tp.2013.81

Abstract

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34 216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10−7). These findings replicate in a second large data set (N=127 274, thereof 76 242 smokers) for both SI (P=1.2 × 10−5) and CPD (P=9.3 × 10−5). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Highlights

Smoking and obesity are major risk factors for many serious diseases.1,2 Eating and smoking are behavioral traits that are at least in part controlled by the same reward mechanisms.3Genome-wide association studies (GWAS) have yielded 32 single-nucleotide polymorphisms (SNPs) associated with body mass index (BMI).4 Smoking and SNPs associated with increased smoking quantity have been shown to correlate with lower BMI.5,6According to the World Health Organization (WHO), more than one billion people smoke and over 400 million people are obese (BMI 430 kg m À 2), with both prevalences rising
To study the correlation between obesity variants and smoking phenotypes, we focused on the 32 SNPs associating with BMI
The correlations between the set of 32 BMI SNPs and the two smoking variables were significant in this replication sample with P 1⁄4 1.2 Â 10 À 5 and 9.3 Â 10 À 5, for smoking initiation (SI) and cigarettes smoked per day (CPD), respectively

Summary

Introduction

Smoking and obesity are major risk factors for many serious diseases.1,2 Eating and smoking are behavioral traits that are at least in part controlled by the same reward mechanisms.3Genome-wide association studies (GWAS) have yielded 32 single-nucleotide polymorphisms (SNPs) associated with body mass index (BMI).4 Smoking and SNPs associated with increased smoking quantity have been shown to correlate with lower BMI.5,6According to the World Health Organization (WHO), more than one billion people smoke and over 400 million people are obese (BMI 430 kg m À 2), with both prevalences rising (see url section). We report how variants correlating with BMI influence smoking behavior. A generalized form of linear regression was used to test the correlation between quantitative traits (BMI and height) and smoking phenotypes (CPD and SI) in Iceland.

Results

Conclusion