Omics data suggests larger effect of smoking on body mass index than previously thought

Smoking-related DNA methylation patterns explain around a fifth of the variation in body mass index (BMI) between individuals, according to a study publishing September 9^th in the open-access journal PLOS Genetics, led by Carmen Amador at the University of Edinburgh.

Amador and colleagues analyzed genomic sequence data from over 390,000 white British participants enrolled in the Generation Scotland or UK Biobank databases to investigate how tobacco smoking and genetics interact to influence BMI and other obesity-related traits. They found that self-reported smoking status explained 2% of variation in BMI, while genetics accounted for 50% of the variation, and a further 10% was explained by the interaction between smoking status and genetics. They also found that sex played an important role: the interaction between genetics and smoking explained more of the variance in traits such as weight and body fat percentage in men than in women. For a subset of 8,821 Generation Scotland participants, the researchers repeated the analysis using DNA methylation data as a measure of tobacco exposure. They found that methylation status at 62 methylation sites previously been linked to tobacco consumption was able to explain 22% of the variation in BMI between individuals.

Body mass index is known to have a large genetic component, but the contribution of environmental factors is less well understood. The authors say that biomarkers like DNA methylation may be more accurate proxies for environmental factors than self-reported data and could be used to investigate the influence of other difficult-to-measure lifestyle variables on diseases like obesity.

Amador adds, “Our study highlights the potential of using biomarkers as a measure of an individual's past environment and lifestyle and also suggests that the environment we experience may have long-term effects by altering the way our genetic makeup influences our health and related traits.”

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In your coverage please use this URL to provide access to the freely available article in PLOS Genetics:

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009750

Citation: Amador C, Zeng Y, Barber M, Walker RM, Campbell A, McIntosh AM, et al. (2021) Genome-wide methylation data improves dissection of the effect of smoking on body mass index. PLoS Genet 17(9): e1009750. https://doi.org/10.1371/journal.pgen.1009750

Funding: The authors want to acknowledge funding from the Medical Research Council UK (MRC, https://mrc.ukri.org/funding/): MC_UU_00007/10, MC_PC_U127592696, MC_PC_U127561128; the BBSRC (https://bbsrc.ukri.org/funding/): BBS/E/D/30002275, BBS/E/D/30002276, and a Wellcome Trust (https://wellcome.org/grant-funding) Investigator Award to AMM: 220857/Z/20/Z. YZ was supported by the General Program of National Natural Science Foundation of China (81971270) and Sun Yat-sen University Young Teacher Key Cultivate Project. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) Reference 104036/Z/14/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.