The genetics of O

Because this post is without data, it is certain to be disappointing to many. Nonetheless, investigation begins somewhere - a thought, an idea, a simple observation - and then may blossom into a complete project. Speaking of which, it would be a rather involved project to collect all published data and all of our unpublished observations regarding the genetics of O - overweight vs. obesity.

People who know our work, know that we have examined a lot of genotype-phenotype associations. While overweight/obesity is not our forte in the manner that blood lipids are, suffice to say that we have spent a fair amount of effort looking at genetic factors contributing to BMI. See, for example, this paper on APOA2 and this on PER2, relating chronobiology to obesity. Others have shown that variants in genes FTO, MC4R, LAMA2, SOX6, NEGR1, NPC1, TMEM18 and many others contribute to the risk of obesity.

Our basic observation is - we rarely see a genetic variant that associates with both overweight and obesity. Here, overweight in most populations is defined as a body mass index, or BMI, between 25 and 30 kg/m² (where the kg reflects body weight in kilograms and m² is the square of body height in meters). Obese is a BMI above 30. For some populations, these numbers are different due to different basic characteristics of body size.

So, what could this observation imply? My personal opinion is one centered on differences in the metabolic and biochemical (inflammation, adipocytokine) profiles of adipose tissue in the overweight vs. the obese individual. Thus, there may be an entirely different set of genetic variants, in combination with lifestyle choices of diet, exercise, lark-vs-owl chronotype and such, that contribute to the overweight situation compared to those that magnify the condition to one of obesity.

To me, this is an interesting topic and I would greatly appreciate your thoughts and comments.