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Open Access Highly Accessed Research article

Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study

Megan D Fesinmeyer1, Kari E North23, Unhee Lim4, Petra Bůžková5, Dana C Crawford6, Jeffrey Haessler1, Myron D Gross7, Jay H Fowke8, Robert Goodloe6, Shelley-Ann Love3, Misa Graff3, Christopher S Carlson1, Lewis H Kuller9, Tara C Matise10, Ching-Ping Hong11, Brian E Henderson12, Melissa Allen6, Rebecca R Rohde3, Ping Mayo6, Nathalie Schnetz-Boutaud6, Kristine R Monroe12, Marylyn D Ritchie6, Ross L Prentice1, Lawrence N Kolonel4, JoAnn E Manson13, James Pankow11, Lucia A Hindorff14, Nora Franceschini3, Lynne R Wilkens4, Christopher A Haiman12, Loic Le Marchand4 and Ulrike Peters1*

Author Affiliations

1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, PO Box 19024, Seattle, WA 98109-1024, USA

2 Carolina Center for Genome Sciences, School of Public Health, University of North Carolina, Chapel Hill, NC, 27514, USA

3 Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA

4 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA

5 Department of Biostatistics, University of Washington, Seattle, USA

6 Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, 37203, USA

7 Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, 55455, USA

8 Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, 37203, USA

9 Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

10 Department of Statistics & Biostatistics, Rutgers University, Piscataway, NJ, 08854, USA

11 Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA

12 Department of Preventive Medicine, Keck School of Medicine / Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

13 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

14 Office of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

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BMC Medical Genetics 2013, 14:6  doi:10.1186/1471-2350-14-6

Published: 11 January 2013

Abstract

Background

Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.

Methods

As part of the ‘Population Architecture using Genomics and Epidemiology (PAGE)’ Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses.

Results

We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, pinteraction = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5x10-5), vs. former/never smokers (β = 0.006, p = 0.05, pinteraction = 0.08).

Conclusions

These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results.

Clinical Trial Registration

NCT00000611

Keywords:
Obesity; Body mass index; Genome-wide association study; Genetic risk factor; Smoking interactions; Genetic epidemiology