Doctors at King's College London showed changes hardwired into some people's DNA altered the way they processed fats and sugars and may make it easier to starve their bodies.
The eating disorder charity Beat said the findings were groundbreaking.
Anorexia is an eating disorder that leads people to lose as much weight as possible by eating little and sometimes exercising excessively.
People with anorexia often have a distorted image of themselves and can feel fat even if they are dangerously underweight.
It is more likely to affect young women but can affect anyone of any age or gender.
In the long term, anorexia can damage muscles, bones, the heart, fertility and can be fatal.
It can be treated and people can make a full recovery.
The researchers looked at 16,992 people with anorexia and 55,525 people without the disease, from 17 countries.
All their DNA - the blueprint for the human body - was analysed to find mutations in genetic instructions that were more common in anorexia patients.
The study, published in Nature Genetics, found some mutations also presented in other psychiatric disorders such obsessive-compulsive disorder, anxiety, and schizophrenia.
But they also found mutations in the instructions that control the body's metabolism, particularly those involving blood sugar levels and body fat.
"There is something in those systems that has gone awry," Prof Janet Treasure, from the Institute of Psychiatry at King's College London, told BBC News.
The researchers - at King's and the University of North Carolina at Chapel Hill - say anorexia should now be considered a "metabo-psychiatric disorder" as it is a disease of mind and body.
The researchers have not fully explored the role played by the genetic instructions they discovered.
However, they suspect the mutations allow people to starve their bodies for longer.
When most people lose weight, there are signals in the body that push back, stimulating the appetite..
"These are very important in controlling the set-point of weight," Prof Treasure told BBC News.
"It's possible that when people lose weight with anorexia nervosa, they haven't got such strong drivers getting the set-point back to normal."
"It's very significant because there's been difficulty knowing what sort of disorder anorexia is," Prof Treasure told BBC News.
"There have been swings in our understanding
"Now, we know it's a complex mixture of aspects from the body and the mind that interact and cause this complex disorder."
Knowing anorexia was a mix of the physical and the mental could persuade patients to have treatment, she added.
Andrew Radford, the chief executive of Beat, said: "This is groundbreaking research that significantly increases our understanding of the genetic origins of this serious illness.
"We strongly encourage researchers to examine the results of this study and consider how it can contribute to the development of new treatments so we can end the pain and suffering of eating disorders."