De novo deleterious variants that may alter the dopaminergic reward pathway are associated with anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. Up to now, four genome-wide association studies of AN have been conducted to date and identified only few significant loci. However, both previous studies focused on common variation and on rare exonic variants. Currently, de novo variants are one of the most significant risk factors for neurodevelopmental disorders and psychiatric disorders.

METHODS

We analyzed by whole exome sequencing a cohort of nine female AN individuals and their parents (mother and father), and focused our analysis on de novo variants.

RESULTS

Here, we found seven de novo missense variants in potential genes in nine studied AN patients. Four of these genes (CSMD1, CREB3, PTPRD and GAB1) belong to a same signaling pathway involving neuron differentiation and dopamine pathway.

CONCLUSIONS

This study provides a list of interesting genes such as CSDM1 and CREB3 that are candidates to be involved in the etiology of anorexia nervosa.

LEVEL OF EVIDENCE: basic research.