There's been a flurry of research recently trying to pin down a single gene that could be responsible for obesity, but the fact is genes don't work like that. Despite strong evidence for specific genes accounting for some types of hereditary or severe obesity, the reality is that excessive weight gain can be founded in a variety of different mechanisms, from an inability to regulate appetite to a dysfunction in energy expenditure. A new large-scale study combing through the genetic data of more than 700,000 individuals has now identified 14 genetic variations associated with obesity and body mass index (BMI).

"By considering the genes as a group rather than one-by-one, we could highlight specific genes that both had strong support from genetics and that likely carry out functions that we predict to be important in controlling body weight," says Joel Hirschhorn Professor of Genetics at Boston Children's Hospital and Harvard Medical School.

The massive study involved over 250 research institutions from around the world and combined data from 125 different studies and 718,734 subjects. Fourteen specific genetic variants in 13 genes were identified as playing an important role in the control of body weight, and eight of the genes are new targets for obesity research.

One of the discoveries was a copy variation in a gene called MC4R. The gene variant, found in almost 1 in 5,000 people, affects the production of a protein that regulates appetite and results in carriers weighing an average of 15 lb (6.8 kg) heavier than those without the genetic variant. Another discovery revealed two variants in the GIPR gene, found in about 1 in 400 people, and corresponding with an average of 4.5 lb (2 kg) more weight than non-carriers.

"Our study has provided new potential targets for therapeutic interventions, and may even help personalize treatment for carriers of the genetic variations," says Ruth Loos, lead on the study. "While we are a few steps closer to understanding the biology of why some people gain or lose weight more easily than others, further research on each of the identified genes is needed to understand the mechanisms through which they act."

The study was published in the journal Nature Genetics.

Source: Mount Sinai