Scientists may have identified the first genetic link to being underweight. A paper published in the journal Nature this week found that people with extra copies of a region of chromosome 16, locus 16p11.2, have a significantly increased risk of being underweight.
Researchers from Imperial College London and the University of Lausanne in Switzerland studied a large group of patients with developmental and intellectual disabilities. They found that men who had a duplication of locus 16p11.2 were 23 times and women five times more likely to be underweight than those who did not.
Underweight patients had a body mass index (BMI) of less than 18.5, whereas healthy people have BMIs between 18.5 and 25. This follows previous observations that people who are missing this same genetic locus are at an increased risk of being morbidly obese.
In general, people have two copies of each gene, one from each parent. However, it is not uncommon for a copy to be deleted or duplicated. Often this has no visible effect but having too few or too many copies of certain genes can sometimes lead to disease.
Professor Philippe Froguel from Imperial's School of Public Health, who led the research, said it is the 'first example of a deletion and a duplication of one part of the genome having opposite effects'.
Locus 16p11.2 contains 28 genes, any of which could be responsible for the effects on body weight. 'We now plan to sequence these genes and find out what they do, so we can get an idea of which ones are involved in regulating appetite', Professor Froguel said.
The Nature paper also showed a strong link between this locus and head size. A quarter of patients with a duplication of 16p11.2 had microcephaly, where the head is abnormally small, whereas those with a deletion of the locus had larger heads.
This is consistent with the known link between this group of genes and cognitive disorders, which could be related to impaired brain development. Head size was also correlated with BMI.
'This is the first genetic cause of extreme thinness that has been identified. One reason this is important is that it shows that failure to thrive in childhood can be genetically driven. If a child is not eating, it's not necessarily the parents' fault', Professor Froguel said.