High-impact rare genetic variants in severe schizophrenia.

ABSTRACT: Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10^-5) and damaging missense variants in intolerant genes (odds ratio, 2.9

SUBMITTER: Zoghbi AW 

PROVIDER: S-EPMC8713775 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature