From saliva samples, the team used DNA analysis to reveal previously unknown regions of the human genome associated with healthy thinness.
They found that approximately three quarters of people in this cohort had a family history of being thin.
Meanwhile, comparison with 1,985 severely obese participants showed additional genes connected with poor weight control, a finding that indicated "the genetic dice are loaded against them", according to the study.
Prof Sadaf Farooqi, who led the research, said: "It's easy to rush to judgment and criticise people for their weight, but the science shows that things are far more complex.
"We have far less control over our weight that we might wish to think."
Numerous studies have looked in depth at the genetics of obesity, but few have concentrated so closely on people at the thin end of the BMI scale.
The results significantly shift the debate on the causes of healthy thinness towards heritability and away from lifestyle factors.
The scientists said their data could also provide genetic targets for future drug treatments to combat obesity.
"This research shows for the first time that healthy people are generally thin because they have a lower burden of genes that increase a person's chances of being overweight and not because they are morally superior, as some suggest," Prof Farooqi added.
"We already know that people can be thin for different reasons. If we can find the genes that prevent them from putting on weight, we may be able to target those genes to find new weight- loss strategies and help people who do not have this advantage."
More than six in 10 adults in the UK are currently overweight, which means they have a BMI of 25 to 29, while one in four adults is obese, meaning a BMI of 30 and above.
By the age of five, one in four children is either overweight or obese, according to figures from NHS Digital.
