Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

Just in time for the start of Obesity Canada’s Biennial Canadian Obesity Summit in Ottawa (April 23-26, 2019), where the issue of obesity as a multifactorial complex disease will be front and centre of discussions (both in terms of prevention and management), comes a landmark publication by a team of US obesity researchers published in CELL.

The paper describes the development and validation of a cumulative “obesity score” based on the presence of common DNA variants that can affect body weight.

This polygenic predictor, looking at over 2.1 million common variants to quantify this susceptibility was tested in more than 300,000 individuals ranging from middle age to birth.

Among middle-aged adults, the researchers found a 13 kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles.

Most interestingly, in terms of childhood obesity, a longitudinal analysis of a birth cohort, showed minimal differences in birthweight across polygenic score deciles, but a significant gradient in early childhood that reached 12 kg by 18 years of age. 

These observations not only support the notion of the polygenic nature of “garden-variety” obesity, but also, that having more of the obesity susceptibility alleles dramatically predisposes individual to the future development of obesity.

In fact, as the authors point out, the effect of a high polygenic score can be similar to having a rare, monogenic form of obesity.

So while it may well be the environment that pulls the trigger, it is most certainly the genes that load the gun.

Clearly, it is high time we abandon the judgemental “shame and blame” approach to dealing with obesity, where people who are at a “healthy” weight are held up as “model citizens”, versus the “irresponsible” people with excess weight, who simply chose to be fat.

Obviously, whether or not in our current obesogenic environment someone develops obesity, is largely the “luck of the (genetic) draw”.

@DrSharma
Ottawa, ON

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