Leveraging shared genetic risk for schizophrenia and anorexia nervosa to understand clinical heterogeneity

Schizophrenia (SCZ) and anorexia nervosa (AN) are severe psychiatric disorders with insufficient treatments and an unexpectedly high genetic correlation.

To further investigate this genetic relationship and the clinical impact of shared genes, we aim to:1) Use conjunctional FDR to identify shared genomic risk loci for SCZ and AN using data from the Psychiatric Genomics Consortium (94 390 total cases)2) Quantify the impact of AN and SCZ-AN genomic risk on the clinical presentation and outcome of SCZ in 10 827 cases from the Swedish Schizophrenia Study (S3; PI: Sullivan)3) Quantify the impact of SCZ and SCZ-AN genomic risk on the clinical presentation and outcome of AN in 6187 cases from the Eating Disorder Genetics Initiative (EDGI; PI: Bulik)4) Define relationships between SCZ-AN genomic risk and other medical outcomes by conducting a PheWAS in individuals without either disorder from S3 and EDGI (N=18 532) and the UK Biobank (N=400k)  The project involves 5-years of international and local collaboration with clinical and basic researchers specializing in SCZ (PI Bergen-KI; Prof.

Sullivan-KI/UNC) or AN (Dr. Baker-UNC; Prof. Bulik-KI/UNC; Dr.

Birgegard-KI).Successful completion of these aims will identify genetic risk loci for SCZ-AN, the ways these loci modify clinical features of SCZ and AN, and their impact on risk for other medical problems. These results can be leveraged to improve outcomes for two difficult to treat and deadly psychiatric illnesses.