Several genetic markers associated with the disorder anorexia nervosa (AN) have been identified. American researchers carried out the first, large-scale genome-wide a association study (GWAS) for AN. The study identified small variations in the DNA of AN patients called SNPs (single nucleotide polymorphism), as well as larger DNA deletions or replications called copy number variations (CNVs).
'Despite various genetic studies that identified a handful of candidate genes associated with AN, the genetic architecture underlying susceptibility to AN has been largely unknown', said Dr Hakon Hakonarson who led the study at The Children's Hospital of Philadelphia. 'This is the first genome-wide association study on a large anorexia cohort, as well as the first study of copy number variations in the disorder'.
Anorexia nervosa affects one in every 200 British women and 2,000 British men. Symptoms usually first present during adolescence and include a refusal to eat, severe weight loss, an irrational fear of gaining weight and a distorted view of their body image. AN has the highest mortality rate of all psychiatric disorders.
This latest study scanned the genomes of 1,003 adult AN patients and compared them to a control group of 3,733 children who did not have AN. SNPs associated with AN were found in the gene OPDR1 and close to the gene HTR1D, confirming the results of previous AN studies.
A novel SNP was also identified in between the genes CHD9 and CHD10. These genes encode proteins called cadherins, which are required for proper communication between nerve cells. This region of the genome has previously been associated with the psychiatric disorder autism. 'The fact that they come up now in this disease, which is another sort of neural psychiatric disease, is in my view, very intriguing', said Dr Hakonarson.
In addition to the SNPs identified in AN patients, a genetic deletion was also identified in a region of chromosome 13. This CNV was found to occur ten times more often in AN patients than in the control group and has prompted further analysis in the future.
'Our study suggests that both common SNPs and rare CNVs contribute to the pathogenesis of anorexia nervosa. The gene variants we discovered are worthy of further analysis in independent cohorts. However, the relatively modest number of anorexia cases explained by these results we found suggests that many other candidate genes remain unknown', said Dr Hakonarson. 'Future studies will require much larger sample sizes to detect additional gene variants involved in this complex disorder'.
The research was published in Molecular Psychiatry.