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In Drug Development, Think Beyond the Genome

Interesting news for those thinking about personalized medicine and drug development: children born to mothers after bariatric gastrointestinal bypass surgery are set up for a healthier life than their pre-surgery older siblings, due to differential methylation of their DNA.1 This recent study proves a good reminder that the environment exerts a powerful effect on our epigenetics, our transcriptome, and therefore our phenotype. As such, advanced drug development efforts should consider more than just genetic mutations.

A recent study demonstrated that changes to the maternal environment result in epigenetic differences between siblings

To demonstrate environmental impact on the epigenome, the study compared DNA methylation of siblings born to mothers pre- and post-bariatric surgery.1 They found more than 5,000 genes that were differentially methylated between siblings born before versus after bariatric surgery.1 The genes fell into three broad disease categories: metabolic and gastrointestinal/endocrine diseases (eg. diabetes), inflammatory diseases (eg. arthritis), and cardiovascular diseases (eg. heart disease). The methylation changes play out as might be expected; kids born to mothers following bypass surgery are healthier. They are less obese, with improved cardiometabolic profiles.

Studies involving the contained environment of the womb provide a concrete example of the environment’s impact on gene expression. It is already known that maternal diet affects children’s glucose homeostasis through epigenetic changes.2 This article provides more evidence that environmental differences have direct and profound bearing on our propensity towards disease, and can be extrapolated to strengthen the argument that the human genome is not the whole picture.

Pharmaceutical companies are investing more of their drug development dollars in understanding the genetic basis of disease, as evidenced by Amgen’s recent purchase of Decode, a company that has tried to match up genetic variants with disease.3 While personalized medicine holds the promise of better and more effective drugs, we shouldn’t expect such a drug development approach to be the silver bullet. Biology, of course, continues to prove more complicated than that.

  1. Guenard F, et al. Differential regulation of glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. PNAS 2013 Jul 9;110(28):11439-44. doi: 10.1073/pnas.1216959110
  2. Godfrey KM, et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60(5): 1582-1534.
  3. Hirschler B. Amgen buys Icelandic gene hunter Decode for $415 million. Reuters. Dec 10, 2012.