B3253 - Inclusion of ALSPAC samples in Psychiatric Genomics Consortium PGC for ED - 14/01/2021

B number: 
B3253
Principal applicant name: 
nadia Micali | University of geneva, Switzerland; UCL, UK
Co-applicants: 
Cynthia Bulik, Gerome breen, Mohamed Abdulkadir, Jonathan Coleman, Melissa Anne Munn-Chernoff, Jet Termorshuizen, Sang Hyuck Lee
Title of project: 
Inclusion of ALSPAC samples in Psychiatric Genomics Consortium (PGC) for ED
Proposal summary: 

Eating disorders (ED) such as anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) are common psychiatric disorders with life-long health impacts. Additionally, current treatment options have limited effectiveness, highlighted by the observation that only 30% of adult patients with AN fully recover. The development of EDs is highly complex and driven by environmental and genetic factors. Previous research has suggested that EDs run in families, but the specific genetic variants associated with risk for EDs are not well understood. Twin studies have shown that the heritability for EDs ranges from 40%-70%. Similarly, to other psychiatric disorders, such as depression or schizophrenia, many genetic variants with relatively small effect underlie the overall genetic risk for EDs. Due to the nature of these effects, extremely large sample sizes are necessary which can only be amassed by international efforts. For AN previous large scale genetic studies, comparing patients with healthy controls, have been successful in pinpointing genetic variants associated with the illness (Duncan et al., 2017). However, no such attempts have been made regarding BN or BED and the field of EDs is lacking behind the genomic discovery of other psychiatric disorders. The success of these studies, which search across the entire genome to find associated genetic markers, is highly dependent on the number of patients and controls included in the research because the sample sizes defines the statistical power to detect significant associations. Thus, worldwide joint forces are necessary to combine datasets to boost sample sizes. Therefore, we propose to include ALSPAC participants in the international approach: Using the rich database of ALSPAC to identify patients diagnosed with AN, BN or BED and add them to international cohorts examining the genetic architecture of EDs. The findings may provide a better understanding of the development of EDs and may help to identify or new treatment strategies including potential targets for pharmaceutical treatment.

Impact of research: 
The identification of genomic variants associated with EDs may enable researcher to understand the underlying biology and may ultimately inform the development of new treatments. Only one FDA-approved medication targets the core symptoms of an eating disorder (in this case binge eating) and mortality is high. An international collaboration lead by the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) with the Anorexia Nervosa Genetics Initiative (ANGI) and iPsych (Denmark) has found eight loci for anorexia nervosa with promising single gene loci being potential druggable targets. We also see that anorexia has strong psychiatric and metabolic genetics, suggesting a reconceptualization of the illness is needed. We seek to perform a meta-analysis of our GWAS results with ALSPAC to extend genomic discovery in all eating disorders. We aim to improve detection, prevention, and ultimately to develop cures to reduce and ultimately eliminate mortality from eating disorders.
Date proposal received: 
Monday, 21 December, 2020
Date proposal approved: 
Thursday, 14 January, 2021
Keywords: 
Genetics, Eating disorders - anorexia, bulimia