1 2 21 brain out12/14/2023 Functional analyses of shared loci revealed enrichment for biological pathways of the nervous and immune systems. Using conjFDR, 70 unique loci were shared between IBS and psychiatric disorders. We identified 132 independent IBS-associated loci (condFDR < 0.05) by conditioning on psychiatric disorders ( n = 127) and gastrointestinal diseases ( n = 24). We found extensive polygenic overlap between IBS and psychiatric disorders and to a lesser extent with gastrointestinal diseases. ![]() IBS was highly polygenic with 12k trait-influencing variants. We used functional mapping and gene annotation (FUMA) for functional analyses. We leveraged identified genetic overlap to boost the discovery of genomic loci associated with IBS, and to identify specific shared loci associated with both IBS and psychiatric and gastrointestinal phenotypes, using the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework. Using GWAS summary statistics of IBS (53,400 cases and 433,201 controls), and psychiatric and gastrointestinal phenotypes, we performed bivariate casual mixture model analysis to characterize the genetic architecture and genetic overlap between these phenotypes. Here, we characterize the genetic architecture of IBS, further, investigate its genetic overlap with psychiatric and gastrointestinal phenotypes, and identify novel genomic risk loci. However, most of the heritability remains unidentified, and the genetic overlap with psychiatric and somatic disorders is not quantified beyond genome-wide genetic correlations. A recent genome-wide association study (GWAS) identified several genetic risk variants for IBS. Irritable bowel syndrome (IBS) often co-occurs with psychiatric and gastrointestinal disorders.
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