Who Cares About GWAS? Should We?

GWAS is an acronym that’s hard to avoid if you read much about obesity research. It’s shorthand for genome-wide association studies. And for the last several months, some of the brightest people in obesity research have been debating the merits of hammering away at GWAS that focuses on BMI. Does GWAS research miss the mark because it focuses on BMI? Or instead, are these studies a treasure trove of insights?

Point Counterpoint

This all started with a narrative review and an invited counterpoint in the International Journal of Obesity. The authors are some of the best scientists in the field. So we have a serious debate about ideas and facts – not heated arguments that stray into logical fallacies for the sake of “winning.”

The Corrupting Influence of BMI

In the review that started all of this, Manfred Müller and colleagues offer a sharp critique of GWAS that focuses on BMI. They argue these studies have done little to explain the physiology of weight regulation. In part, they say, that’s because BMI is such a crude measure of adiposity. It’s simply an inadequate measure for such a phenotype that presents with so many variations.

On top of that, they say that GWAS has been unfocused because we’re still lacking solid concepts for body weight regulation. Without stronger fundamental concepts, scientists are essentially probing blindly while using inadequate tools for their probes.

A Crude, but Productive Tool

In their counterpoint, John Speakman and colleagues describe a treasure trove of fundamental insights into the genetic basis of obesity. They point out that GWAS has produced discoveries of more than 200 genes related to obesity. They add that discovering how these genes work has been even more important. Most of them act centrally, in the brain, and not peripherally.

“Nobody will argue with the suggestion that BMI can be a poor measure of adiposity at the individual level,” they write. But they argue that the power of large samples that are possible with BMI can overcome these problems in many cases.

Embracing Complexity – and Ambiguity

Working in obesity requires quite a bit of humility. Even as we learn a lot, we learn that we’re living with a great deal of complexity that we don’t fully understand. Thus, without overstating their case, Müller et al responded recently to the counterpoint with thanks for that counterpoint. It opens an overdue discussion, they say.

In the process, they make some excellent points about the interaction of environment and the genome. This needs more attention. We also need a better framework for understanding exactly how the regulation of body weight works.

These three papers offer an outstanding briefing on much of what we do and don’t understand about obesity. Even more important, they offer a model for scholarly debate, free from logical fallacies that infect so many other hot topics in obesity and nutrition research.

You’ll find all three parts of this debate here, here, and here.

Caring Hands, photograph © Stephen Poff / flickr

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December 16, 2018