An Evolutionary Perspective on the Genetics of Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a serious psychiatric disorder that typically emerges around adolescence and predominantly affects girls and women. Recent progress has been made in identifying biological correlates of this debilitating disorder, but more research is needed to pinpoint the specific mechanisms that lead to the development and maintenance of AN. There is a known phenotypic link between AN and growth as well as sexual maturation, yet the genetic overlap between these phenotypes has never been investigated in detail. One may hypothesize that shared factors between AN, energy metabolism and reproductive functions may have been under recent evolutionary selection. Here, we characterize the genetic overlap between AN, BMI and age at menarche, and took an evolutionary perspective, aiming to reveal potential evolutionary factors that may help explain the origin of AN in recent human evolution. We obtained publicly available GWAS summary statistics of AN, BMI and age at menarche and studied the polygenic overlap between them. We found 22 loci overlapping between AN and BMI, and 9 loci between AN and age at menarche, with twelve of these not previously associated with AN. Next, we used Neandertal Selective Sweep scores to explore potential positive evolutionary selection for loci associated with the three phenotypes, or overlapping between them. We found evidence that gene variants associated with AN may have been under particular evolutionary dynamic. The circadian cycle seemed to be highly relevant to the studied genetic overlaps and prone to recent evolutionary selection, offering a promising avenue for future research into chronobiology. Taken together, our findings contribute to the understanding of the genetic underpinning of AN. Ultimately, better knowledge of the biological origins of AN may help to target specific biological processes and facilitate early intervention in individuals who are most at risk.