The Genetics of Obesity – Recent Developments

Dude, you are way overweight

What is the relationship between research into the genetics of obesity—so-called “fat gene” research—and fatlogic? Is the science as meaningful as its proponents believe, or only a relatively minor piece of the obesity puzzle? Has progress in this field been co-opted by patients and untreated “fat acceptance” types who are all too happy to place responsibility anywhere but in their own hands?

Family studies pointed the way to realization that genes play a significant role in a person’s likelihood of becoming obese, but also left many unanswered questions. In 2012, the Journal of the American Academy of Pediatrics offered its readers an update on the current state of genomics and made a prediction:

Next-generation sequencing techniques are expected to fill the gap of “missing heritability” of obesity, identifying rare variants associated with the trait and clarifying the role of epigenetics in its heritability. Pediatric obesity emerges as a complex phenotype, modulated by unique gene–environment interactions that occur in periods of life and are “permissive” for the programming of adult obesity.

A study from Brigham Young University looked at the differences in Body Mass Index percentiles between identical twins, between non-twin siblings, and between random pairs of non-siblings. Professor Joe Price pointed out that while people are used to thinking in terms of “fat families and skinny families,” there is actually a lot of variation within families. Siblings with ostensibly the same basic heredity and upbringing turn out differently, and there must be a reason.

A Cumulative Effect

The 32 genes that had, up until last year, been identified as obesity risk factors could only account for somewhere around two percent of individual differences. This baffled researchers and led to the coining of the term “missing heritability.”

The study’s lead author, Clare Llewellyn, PhD, and others at University College London used a new method, Genome-Wide Complex Trait Analysis. The results suggest that concentrating on individual genes can be misleading. Instead, the researchers concluded that it is necessary to look at the additive effects of “multiple genes across the whole genome,” which can account for as much as 30% of individual differences. Dr. Llewellyn told the press:

These findings are important because they confirm that in children genes play a very important role in determining body weight. At present only a few genetic variants have been discovered…. These findings suggest there are hundreds of other genetic variants influencing body weight that are yet to be discovered.

Sadaf Farooqi, Professor of Metabolism and Medicine at University of Cambridge, has discussed similar findings. His work was part of the UK10K Project, an extensive research initiative that had already discovered several genes linked to early onset childhood obesity.  He discusses the synergistic effect of genes on obesity:

Some children will be obese because they have severe mutations, but our research indicates that some may have a combination of severe mutations and milder acting variants that in combination contribute to their obesity.

One thing about this quest for new genetic variants is important: it began, as far as possible, with a clean slate. The subjects whose genes are examined by the project are 1000 severely obese children – of whom none show any of the already-known obesity-related gene mutations.

Your responses and feedback are welcome!


Source: “Genetics of Pediatric Obesity,” aappublications.org, June 4, 2012
Source: “Trio of studies examine obesity in American families,” MedicalXpress.com, July 18, 2012
Source: “Genetic variants influence childhood obesity, say researchers,” News-Medical.net, March 27, 2013
Source: “ Study Identifies Four New Genetic Markers For Severe Childhood Obesity,” Time.com, April 12, 2013
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