Sex- and gender-sensitive analysis of genetic mechanisms in body weight regulation with regard to eating disorders and obesity 

Body weight regulation is a complex biological process that is shaped by an interplay of environmental and genetic factors (Hinney et al., 2022). Large genome-wide association studies (GWAS) have identified a large number of genetic variants, mainly single nucleotide polymorphisms, that are associated with diseases such as anorexia nervosa (AN; Watson et al., 2019) or the variance of the body weight as measured by the body mass index (BMI; Hinney et al., 2007; Pulit et al., 2019; Yengo et al., 2018).

Our research team is dedicated to investigating genetic mechanisms that influence body weight regulation and the development of obesity and eating disorders. Here, the core emphasis is directed towards the identification and analysis of candidate genes and genetic variants as well as the evaluation of non-coding RNAs, particularly circular RNAs (circRNAs). Classical approaches, such as gene expression analyses, are supplemented by cutting-edge methods, including bioinformatic evaluations of large public data sets (Rajcsanyi, Zheng, et al., 2022) or Mendelian randomization studies (e.g. Dinkelbach et al., 2024; Peters et al., 2021). An important premise underpinning our research is the consideration of sex and gender aspects. This enables a refined interpretation of research findings and eventually a medicine that is personalized to the patient. The fundamental aspiration of our research is to enhance clinical diagnostics and care through a comprehensive and profound understanding of the genetic basis of the diseases.

Key projects and approaches of our research group:

Identification and analysis of candidate genes and genetic variants

At the core of our research lies the identification and analysis of genes and genetic variants that influence body weight regulation (e.g. Giuranna et al., 2024; Rajcsanyi et al., 2023; Zheng et al., 2022; Zheng et al., 2023). Particularly, our analyses are focused on the genes of the leptin-melanocortin-system (Rajcsanyi et al., 2024), given its role in the regulation of food intake. These genes as well as associated genetic variants and mechanisms are being investigated as part of the STAR-GEN (dt. “Starvationsforschung unter Berücksichtigung geschlechtersensibler Aspekte) graduate college funded by the Graute-Oppermann Foundation. Furthermore, we are active members in several international consortia, including the Psychiatric Genomics Consortium (PGC) and the Early Growth Genetics (EGG) consortium. Consequently, we have contributed to the identification of genetic variants associated with AN and (childhood) obesity.

The role of circRNAs in body weight regulation

A substantial proportion of genetic variants identified in GWAS are located in non-coding regions of the genome and therefore have no direct effects on protein structure and function (Giral et al., 2018; Watanabe et al., 2019). However, recent studies suggest that these variants may act indirectly via non-coding RNAs, such as circRNAs (e.g. Ahmed et al., 2019; Liu et al., 2019). Originally, circRNAs were considered a by-product of splicing. However, since the early 2010s, they have been excessively studied as they are now known as functional entities (Barrett & Salzman, 2016). Our research investigates the role of circRNAs in the development of eating disorders and obesity, and explores the potential effects of genetic variants on the expression of these RNA species (Rajcsanyi, Diebels, et al., 2022).