If you listen to genes for warnings of disease risk, you may have noticed that “biopathway genes” tend to shout, and that “lifestyle genes” tend to whisper. Yet both kinds of genes—those directly associated with sequences of unfortunate biological events and those associated with modifiable behaviors—may have independent effects on health outcomes. According to scientists based at the University of Bristol, the lifestyle genes may remain underappreciated, even though they are being identified with greater frequency in genome-wide association studies (GWAS).
In the hope of redressing the imbalance, the scientists discussed the advantages of paying more attention to lifestyle genes. In an article (“G = E: What GWAS Can Tell Us about the Environment”) published February 11 in PLOS Genetics, the scientists considered illustrative examples from tobacco and alcohol research. These examples, the scientists argued, have implications for the interpretation of GWAS results. In particular, the examples indicated that GWAS results may be useful places to look for potentially modifiable risk factors for disease, which could then be targeted by clinicians for interventions.
“As large, richly phenotyped cohort studies emerge, it will become possible to identify modifiable exposures from genetic data and to dissect [independent] pathways within the same cohort,” wrote the article’s authors. “Here, ‘modifiable’ can refer to substance use, but also to factors such as cholesterol or metabolite levels or blood pressure, which are directly influenced by lifestyle choices. A failure to appreciate this point will hamper our ability to translate the results of GWAS into health benefits, by focusing attention on possible biological pathways when, in fact, the target for intervention could be a modifiable environmental or behavioral exposure.”
Professor Marcus Munafo, the study's lead author, said: “Genome-wide association studies of lung cancer have identified genetic variants that strongly predict smoking. It is possible these genetic variants have independent effects on both smoking and lung cancer, but it seems far more likely that this variant was seen because smoking causes lung cancer.”
He continued, saying that “Genetic predictors for lifestyle are still being identified. We already know about variants that predict smoking, alcohol or caffeine use, and research is ongoing to predict things like cannabis use. As larger GWASs of disease are carried out, more of these variants which indicate the causal modifiable risk factors for disease will be identified. This will help the development of more effective and better-targeted interventions.
“These discoveries really underline how valuable the investment in genetic studies is—more so than is often thought. Genetic studies can not only identify the biological risk factors for disease, but the behavioral risk factors as well.”
