Zeynep Yilmaz

Project title

Predicting Severe and Enduring Anorexia Nervosa and Associated Outcomes: Genes and Environment

What is your project about?

Anorexia nervosa is a serious psychiatric disorder that is difficult to treat, may become chronic if not detected and treated early, and profoundly affects multiple aspects of an individual’s functioning. Despite the public health burden, we lack the ability to identify individuals at risk for severe and enduring anorexia nervosa. This project aims to systematically investigate genetic and environmental risk factors associated with anorexia nervosa severity and health-related and social outcomes associated severe anorexia nervosa. Combining epidemiological data from Danish registers with existing genetic data, we propose to develop a continuous measure of anorexia nervosa severity; identify environmental risk factors for severe and enduring anorexia nervosa and associated outcomes; investigate the genetic architecture of anorexia nervosa severity using modern genomic methods; develop multifactorial prediction models of anorexia nervosa severity and related outcomes using genetic and epidemiological data; and examine whether distinct subtypes of severe anorexia nervosa exist based on different risk profiles. Importantly, we will have the unprecedented opportunity to replicate our findings in an independent dataset of anorexia nervosa cases with genetic and epidemiological data in Sweden. Understanding whether different underlying biological processes contribute to different anorexia nervosa courses and outcomes is an essential first step in early identification and personalized treatment.

How did you become interested in your particular field of research?

As a child I was thoroughly fascinated by psychology, and I remember flipping through the pages of encyclopedias and Mayo Clinic books to read about psychiatric disorders. Eating disorders, particularly anorexia nervosa, always fascinated me from a societal and evolutionary perspective. I completed my Honours BSc in Psychology at University of Toronto and then worked as a clinical research coordinator in eating disorders at Toronto General Hospital in Canada. As a part of my job, I had the opportunity to coordinate genetic and biological research studies and conducted clinical assessments of patients with eating disorders. During this period, I learned about the alarming clinical picture associated with anorexia nervosa, as well as the difficulties and suffering experienced by the patients and their loved ones. I decided to pursue my graduate training in psychiatric genomics with the hopes of elucidating the genetic basis of anorexia nervosa to better understand the underlying biology. Over the years, it has become very clear that both genes and environment play a significant role in the development of anorexia nervosa. Putting together this puzzle of different genetic and environmental risk factors with a focus on those who have severe and enduring anorexia nervosa could make a tremendous difference in the lives of millions of individuals worldwide struggling with this deadly psychiatric disorder.

What are the scientific challenges and perspectives in your project?

The aim of this proposal is to systematically investigate genetic and environmental risk factors in the etiology of severe and enduring anorexia nervosa and associated outcomes. We posit a multi-dimensional prediction model that incorporates a broad range of genetic and environmental risk factors for the prediction of anorexia nervosa severity as well as the associated health and social outcomes. We aim to optimize this integration by using machine learning methods in a data-driven manner that removes subjective judgment. One key challenge will be deciding how to best measure anorexia nervosa severity using data from Danish registers, and I am extremely lucky to have experienced clinicians here in Denmark and around the world who have agreed to lend their expertise to this important step. The main hypothesis is that genetic and environmental factors are potential novel predictors of severe and enduring anorexia nervosa and may allow for the identification of those at high risk so that targeted treatments can be implemented earlier, reducing the personal and societal cost this serious illness in Denmark.

What is your estimate of the impact, which your project may have to society in the long term?

Anorexia nervosa is a serious psychiatric disorder with very high mortality. Currently, we take a one-size-fits-all approach to the treatment of anorexia nervosa. Understanding whether different underlying biological processes contribute to different cases, courses, and outcomes is an essential first step in personalization of treatment. Important information lies in understanding the extremes of a distribution, and examining patients with severe and enduring anorexia nervosa may help us discover previously undetected risk factors and map the unique contribution of genetic and environmental factors. This project could provide important clues about the epidemiology, biology, and outcome of anorexia nervosa severity, which could assist with defining meaningful subgroups of patients, developing diagnostic categories informed by biology, and identifying individuals at risk for severe and enduring anorexia nervosa in advance to potentially change course of illness and reduce suffering.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The Sapere Aude grant will provide me with an opportunity to kickstart my research career in Europe by establishing my own research group in neurogenetics, which will allow me to bring all my international research collaborations to Denmark. One of the biggest challenges in the field of eating disorders is identifying who is at risk for poor outcome, and this grant will allow me to conduct an important study that could help with developing multifactorial risk models that could assist with predicting who may develop severe and enduring anorexia nervosa. On a personal note, I have been lucky to have extremely supportive mentors and advocates throughout my career, and I intend to continue this tradition with the next generation of STEM scientists. Since I have trained and resided in multiple countries, it is important to me to encourage applicants from diverse backgrounds (including but not limited to nationality) to join my team to ensure inclusivity and representation of diverse experiences and points of view, and I am confident that this prestigious Sapere Aude program will help me recruit the best and the brightest trainees in Denmark and around the world to my research group at Aarhus University.

Background and personal life

To date, I have had the privilege to live in four countries: I was born in the US, grew up in Izmir (Turkey), spend most of my adult life in Canada where I completed my BSc and PhD, and then lived in Chapel Hill (North Carolina, US) where I completed my postdoctoral fellowship and stayed as Assistant Professor before I was recruited to Aarhus University in August 2020. I reside in Aarhus and enjoy leading an active lifestyle that comprises reading, yoga, meditation, climbing, traveling, spending quality time with my friends, and volunteering for causes closely tied to equality and social justice.