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Illuminating Gene–Smoking Interactions Related to BMI.

May 9, 2017
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smokingObesity is a well-known public health problem worldwide. A number of factors are known to be associated with obesity, including genetic factors reported in recent years. But whether genetic effects are modified by environmental or behavioral factors is not well understood.

Now, a large team of international researchers, co-led by School of Public Health biostatisticians, has identified 23 novel genetic loci indicating that tobacco smoking may alter people’s genetic susceptibility to overall fat and body-fat distribution.

In a study published in Nature Communications, the team of researchers evaluated smoking in conjunction with genetic factors and found evidence of gene–smoking interactions on obesity, assessed by body-mass index (BMI) and central obesity measured by waist circumference and waist-to-hip ratio, both adjusted for BMI. The loci identified in the study highlight “novel biological functions, including response to oxidative stress, addictive behavior, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses,” the authors said.

The researchers determined that many of the newly identified loci support the hypothesis that smoking may influence weight fluctuations through appetite regulation, highlighting new biological processes and pathways implicated in the pathogenesis of obesity.

The research team used genomic data from more than 241,000 subjects—51,000 current smokers and 190,000 nonsmokers—to identify the loci. The results were validated in more than 119,000 subjects participating in the UK Biobank. The research identified 6 novel loci for BMI, 11 for waist circumference and 6 for waist-to-hip ratio. Of these, 18 were validated in the UK Biobank data. The identified variants are expressed in brain tissue, as well as adipose tissue, suggesting behavioral mechanisms operating through neurological pathways.

Co-senior author Adrienne Cupples, professor of biostatistics, said the study’s findings are significant because they illuminate mechanisms by which genes may influence addictive behaviors and responses to stress. Of particular interest is a genetic locus that has variants that affect smoking behavior, as well as adiposity traits.  This locus and others warrant further examination, Cupples said.

“The findings show that it is important to consider environmental factors such as smoking in searching for genetic factors affecting adiposity traits and other traits,” she said.

Co-lead authors on the study include: Anne Justice of the Gillings School of Global Public Health, University of North Carolina at Chapel Hill; and Virginia Fisher, doctoral student in the biostatistics program. Other SPH authors on the paper include: Ching-Ti Liu, a faculty member in biostatistics and co-senior author on the paper, and Xuan Deng, Elise Lim, Jeremiah Perez, Julius Ngwa, Luting Xue, and Joseph Wu, all current and former doctoral students from the biostatistics program.

—Lisa Chedekel

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