Their work reveals newly discovered genetic regions linked to being very slim.
The international team say this supports the idea that, for some people, being thin has more to do with inheriting a "lucky" set of genes than having a perfect diet or lifestyle.
The study appears in PLOS Genetics.
In the past few decades, researchers have found hundreds of genetic changes that increase the chance of a person being overweight - but there has been much less focus on the genes of people who are thin.
In this investigation, scientists compared DNA samples from 1,600 healthy thin people in the UK - with a body mass index (BMI) of less than 18 - with those of 2,000 severely obese people and 10,400 people of normal weight.
They also looked closely at lifestyle questionnaires - to rule out eating disorders, for example.
Researchers found people who were obese were more likely to have a set of genes linked to being overweight.
Meanwhile, people who were skinny not only had fewer genes linked to obesity but also had changes in gene regions newly associated with healthy thinness.
'Rush to judgement'
Lead researcher Prof Sadaf Farooqi, from the University of Cambridge, called on people to be less judgemental about others' weight.
"This research shows for the first time that healthy thin 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 people like to suggest," she said.
"It's easy to rush to judgement and criticise people for their weight but science shows that things are far more complex.
"We have far less control over our weight than we might wish to think."
Scientists say the next step is to pinpoint the exact genes involved in healthy thinness.
Their longer-term goal is to see if this new knowledge can help shape new weight-loss strategies.
'Genetically different'
Commenting on the research, Prof Tom Sanders, emeritus professor of nutrition and dietetics, at King's College London, said: "This is an important and well conducted study confirming that precocious severe obesity is often genetically determined and showing convincingly that those who are very thin are genetically different from the general population."
But he added: "Most obesity is acquired in adult life and is linked to the obesogenic environment we live in - a sedentary lifestyle and abundant access to calorie-dense foods."
Prof Tim Spector, also from King's College London, said about a third of people in most countries managed to remain thin despite this.
"Some of this is down to genes but other factors like individual differences in lifestyle or gut microbes are likely to also be responsible," he said.
Health experts say whatever your shape or genetic make-up, the age-old advice of a healthy level of exercise and good diet still stands.
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