Genes Influence Body Weight in Smokers and Never-Smokers

Marcus Munafò PhD Professor of Biological Psychology MRC Integrative Epidemiology Unit UK Centre for Tobacco and Alcohol Studies School of Experimental Psychology University of Bristol United KingdomMedicalResearch.com Interview with:
Marcus Munafò PhD
Professor of Biological Psychology
MRC Integrative Epidemiology Unit
UK Centre for Tobacco and Alcohol Studies
School of Experimental Psychology
University of Bristol United Kingdom

Medical Research: What is the background for this study? What are the main findings?

Dr. Munafo: We were conducting an analysis of data on smoking behaviour and body mass index (BMI), in order to better understand the potential causal effects of smoking on different measures of adiposity. Mendelian randomisation uses genetic variants associated with the exposure of interest (in this case smoking) as proxies for the exposure, in order to reduce the risk of spurious associations arising from confounding or reverse causality. As expected, we found that, among current smokers, a genetic variant associated with heavier smoking was associated with lower BMI, providing good evidence that smoking reduces BMI. However, we also unexpectedly found that the same variant was associated with higher BMI in never smokers. This suggests that this variant might be influencing BMI via pathways other than smoking.

Medical Research: What should clinicians and patients take away from your report?

Dr. Munafo: At this stage this research does not have clear clinical implications. Although the finding that smoking reduces BMI still holds, this isn’t the main message of our study, and certainly the health benefits of stopping smoking far outweigh the consequences of any weight gain that may arise from stopping. What it illustrates is that the genetic influences on BMI are complex, and may be obscured in conventional genome wide association studies that do not take into account strong environmental influences on BMI. In principle this research, if confirmed, might give insight into the mechanisms underlying elevated BMI, which in turn might lead to new treatments, but that is some way off at this stage.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Munafo: The results need to be confirmed independently, and at this stage we can only speculate as to the possible mechanisms. This genetic variant is found in a gene that codes for a nicotinic acetylcholine receptor subunit. One explanation for the association with BMI in never smokers is that nicotinic acetylcholine receptors may play a more general role in our response to reward – which could include natural rewards such as food. However, confirming this will require follow-up work, perhaps including mechanistic studies in animal models, as well as further studies in humans.

Citation:

Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers

Amy E. Taylor, Richard W. Morris, Meg E. Fluharty, Johan H. Bjorngaard, Bjørn Olav Åsvold, Maiken E. Gabrielsen, Archie Campbell, Riccardo Marioni, Meena Kumari, Jenni Hällfors, Satu Männistö, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Lise Lotte N. Husemoen, Tea Skaaby, Tarunveer S. Ahluwalia, Jorien L. Treur, Gonneke Willemsen, Caroline Dale, S. Goya Wannamethee, Jari Lahti, Aarno Palotie, Katri Räikkönen, Aliaksei Kisialiou, Alex McConnachie, Sandosh Padmanabhan, Andrew Wong, Christine Dalgård, Lavinia Paternoster, Yoav Ben-Shlomo, Jessica Tyrrell, John Horwood, David M. Fergusson, Martin A. Kennedy, Tim Frayling, Ellen A. Nohr, Lene Christiansen, Kirsten Ohm Kyvik, Diana Kuh, Graham Watt, Johan Eriksson, Peter H. Whincup, Jacqueline M. Vink, Dorret I. Boomsma, George Davey Smith, Debbie Lawlor, Allan Linneberg, Ian Ford, J. Wouter Jukema, Christine Power, Elina Hyppönen, Marjo-Riitta Jarvelin, Martin Preisig, Katja Borodulin, Jaakko Kaprio, Mika Kivimaki, Blair H. Smith, Caroline Hayward, Pål R. Romundstad, Thorkild I. A. Sørensen, Marcus R. Munafò, Naveed Sattar. Stratification by Smoking Status Reveals an Association of CHRNA5-A3-B4 Genotype with Body Mass Index in Never Smokers. PLoS Genetics, 2014; 10 (12): e1004799 DOI: 10.1371/journal.pgen.1004799

 

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