Genetic Variations Highlight the Importance of Metabolic Processes in Anorexia

July 22, 2020 • Research Highlight

Anorexia nervosa, an eating disorder characterized by restricted eating and low body mass index (BMI), is linked with serious complications that can include death. Treatments for anorexia typically focus on the psychological features of the disorder, including distorted body image and a drive to be thin. Still, patient outcomes with these treatments are often poor. Because the consequences of anorexia are potentially fatal, there is a pressing need to identify reliable and effective targets for intervention. A recent genome-wide association study, funded in part by the National Institute of Mental Health (NIMH), suggests that metabolic processes may play an important role in the disorder and offers a promising new avenue for investigation.

To understand the factors that contribute to anorexia nervosa, an interdisciplinary team of researchers led by Cynthia M. Bulik, Ph.D. , combined genetic data from two sources: the Anorexia Nervosa Genetics Initiative (ANGI)  and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) . The resulting dataset, which included 16,992 individuals with anorexia nervosa and 55,525 control participants, allowed the researchers to conduct a genome-wide association study in which they scanned the entire genome to look for genetic variations that are more common among people with anorexia nervosa.

Everyone has variations in the basic building blocks of their DNA that are called single nucleotide polymorphisms or SNPs. Researchers can examine these SNPs to identify areas of the genome, known as loci, that are associated with different traits. Linking loci to the specific genes that underlie a trait is not always a straightforward process, as loci can span large regions of the genome that include many genes with different functions. However, the loci do offer important clues about the genes and biological pathways that are likely to contribute to the disorder.

In this study, Bulik and colleagues identified eight loci that tended to vary between people with and without an anorexia diagnosis. And they found that the genetic basis of anorexia overlapped with a variety of other traits, including certain psychiatric diagnoses, physical characteristics, and metabolic indicators.

For example, the researchers found that the SNP-based variations associated with anorexia were also associated with mental disorders such as obsessive-compulsive disorder, major depressive disorder, anxiety disorders, and schizophrenia. These genetic correlations mirror findings from clinical and epidemiological studies, which have shown that people with anorexia are more likely to have anxiety, depression, and other disorders compared with the general population.

The researchers also found correlations between the anorexia-linked genetic variations and genetic factors that influence certain body measurements, such as lower fat mass and lower body mass index (BMI). And they found a genetic correlation with higher levels of physical activity, which further mirrors clinical findings—physical activity levels are often dangerously high among individuals with anorexia.

Intriguingly, the genetic basis of anorexia nervosa also overlaps with genetic factors associated with metabolic traits, such as insulin resistance, fasting insulin, and type 2 diabetes. For example, some of the same genetic factors that are associated with decreased risk of developing type 2 diabetes are associated with increased genetic risk for anorexia.

Together, these links suggest that the genetic variations that are associated with anorexia may also influence some of the chemical and biological processes in the body that are essential for life.

People with anorexia nervosa often have considerable difficulty maintaining a healthy BMI even when they’re receiving carefully calibrated nourishment as part of their treatment plan—disruptions to metabolism may help explain why. The findings from this study suggest that both metabolic and psychological processes are important factors to consider when studying, developing, and implementing treatments for this serious disorder.

Reference

Watson, H. J., Yilmaz, Z., Thornton, L. M., Hubel, C., Coleman, J. R. I., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Medland, S. E., Ripke, S., Yao, S., Giusti-Rodriguez, P., Anorexia Nervosa Genetics Initiative, Hanscombe, K. B., Purves, K. L., Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan, R. A. H.,…Bulik, C. M. (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, 51, 1207–1214. doi:10.1038/s41588-019-0439-2

Grants

MH109528 , MH109514