Previous research had shown that an extremely rare mutation in the same PCSK1 gene can, all by itself, lead to huge gains in weight, making it the only known source of so-called "monogenetic" obesity.
But a team led by Philippe Froguel of Imperial College London wanted to find out if PCSK1 might lead, in combination with other genetic factors, to more complex and widespread forms of obesity as well.
When they compared the genomes of 13,000 obese individuals of European ancestry to those of a normal control group, the researchers found three mutations in the gene that were far more common among those coping with excess weight.
These same variants were also linked to increased risk of childhood obesity, as well as less extreme weight gain, the study found.
The benchmark for obesity is the body-mass index (BMI), defined as one's weight in kilograms divided by the square of one's height in meters.
A BMI from 18.5 to 25 is considered in the healthy range, from 25 to 30 is overweight, and 30 or higher is obese.
PCSK1 produces an enzyme, called proconvertase 1, that plays a critical role in converting inactive forms of hormones that control appetite and regulate energy metabolism into active forms.
These hormones include insulin and glucagon, involved in the metabolism of sugar and carbohydrates, as well as a third molecule that signals to the brain that one has eaten enough.
"Nearly 25 percent of the population (studied) has a different form of the enzyme that is apparently a little bit more active," Froguel told AFP in an interview.
The study began with 150 families who responded to a public appeal to participate in research on obesity. Each of the families has at least one obese child.
The researchers then expanded to a larger population in France, as well as new cohorts in Denmark, Switzerland and Germany.
Obesity and obesity-related diseases such as diabetes have gained epidemic proportions in many developed economies. The causes are complex, and include sedentary lifestyle along with eating fat and sugary foods.
But a series of recent discoveries has shown that genetics can also play a bigger role than previously thought.
"We all react differently to an environment that is becoming more and more similar, and the reason we react differently is in part genetic in origin. This gene is one cause among others," said Froguel.
"By the end of the year we will probably have identified a total of a dozen genes linked to obesity," he added.
Another gene, called MC4R, that also orchestrates appetite and energy expenditure, was described in a study last month, also in Nature.