Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study
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
BMC Medical Genetics 2013, 14:6 doi:10.1186/1471-2350-14-6Published: 11 January 2013
Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.
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.
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).
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.
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