Study Identifies Genes That Determine Ability to Lose Weight

Regardless of daily exercise and healthy eating, a person’s genes determine their ability to lose or gain weight, according to a new study published in Nature Genetics.

Researchers at the Icahn School of Medicine at Mount Sinai and other institutions of the Genetic investigation of Anthropometric Traits (GIANT) consortium have identified 14 variations in 13 genes that affect an individual’s body mass index (BMI).

“Our study has identified genes that play a crucial role in the neuronal control of body weight. They act in the brain in pathways that may affect people’s food intake, hunger, satiety, etc. Individuals who inherit these genetic variations may find it harder to eat less or stop eating, as compared to those who did not inherit these variations,” Ruth Loos, PhD, professor at The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai, and the lead author of the study, said in a statement. “It is also the first time a genetic association study for BMI identifies genes that act in pathways that affect energy expenditure and fat cell biology.”

Over the past 10 years, 250 research institutions conducted 125 studies with more than 700,000 participants to locate genetic variations regarding obesity and weight gain, making this the largest genetic association study to date.

A risky copy variation, MC4R, was identified in 1 in every 5000 individuals to weigh 15 pounds more than the average individual. Two variants affecting the gene, GIPR, has carriers weighing 4.5 pound less than non-carriers. Approximately 1 in 400 individuals carry this protective copy. The researchers found 8 variations were in genes that indirectly linked to human obesity. Researchers recommend further research be done on the genes ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, and ZNF169.

The study's findings provide new potential targets for interventions and could lead to personalized treatments for people who are genetic carriers, Loos said.

“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,” she concluded.