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- W4387496636 abstract "Schizophrenia (SCZ) and anorexia nervosa (AN) are two severe and highly heterogeneous disorders showing substantial familial co-aggregation. Genetic factors play a role in both, and a high SCZ-AN single nucleotide polymorphism-based genetic correlation has been observed (rg=0.19-0.29). However, little is known about the shared genetic etiology between SCZ and AN. We analyzed recent large genome-wide association studies on SCZ (N = 130,644) and AN (N = 72,517). MiXeR was employed to quantify the polygenic overlap between SCZ and AN. A conditional/conjunctional false discovery rate (FDR) framework was adopted to boost genomic loci discovery for these disorders individually and identify loci jointly associated with both disorders. A bidirectional two-sample Mendelian randomization (MR) analysis was performed to estimate the causal bidirectional relationship between SCZ and AN. We observed a cross-trait genetic enrichment and considerable polygenic overlap (Dice Coefficient = 62.2%) between SCZ and AN. The proportion of variants with concordant effect directions among all variants influencing SCZ and AN was estimated to be 69.9%. Leveraging the overlapping genetic associations, we identified 7 novel loci for AN and 70 novel loci for SCZ at conditional FDR < 0.01. At conjunctional FDR < 0.05, we identified 12 loci jointly associated with two disorders, implicating several genes, such as: CELSR3, RELN, CYP7B1, TSNARE1, NCAM1 and SOX5. GO enrichment analysis implicated synapse organization, protein kinase inhibitor activity, hexosaminidase activity, and kinase inhibitor activity, and the genes are particularly expressed in the cerebellum and pituitary. The MR analysis suggested a two-way causal relationship (SCZ on AN: odds ratio = 1.13, 95%CI: 1.06-1.19, P < 0.001; AN on SCZ: odds ratio = 1.15, 95% confidence interval: 1.05-1.27, P = 0.003) between the two disorders. This study provides novel insights into the relationship between SCZ and AN by revealing their shared genomic loci and offers a window into the biological mechanisms underlying the two disorders." @default.
- W4387496636 created "2023-10-11" @default.
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- W4387496636 date "2023-10-01" @default.
- W4387496636 modified "2023-10-12" @default.
- W4387496636 title "T78. SHARED GENETIC ARCHITECTURE BETWEEN SCHIZOPHRENIA AND ANOREXIA NERVOSA: A CROSS-TRAIT GENOME-WIDE ANALYSIS" @default.
- W4387496636 doi "https://doi.org/10.1016/j.euroneuro.2023.08.362" @default.
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