A transcriptome-wide association study (TWAS) of 7,805 ASD proband-parent trios, which was subsequently replicated using 35,740 independent samples, using eQTL and splicing quantitative trait loci in 12 brain tissues from GTEx and the CommonMind Consortium (CMC) in Huang et al., 2021 identified MSRA as a gene whose transcriptome-wide association with ASD remained significant after a stringent Bonferroni correction for all genes and all tissues in the analysis (meta-analysis P-value 2.05E-07 in CMC DLPFC-splicing tissue). MSRA had previously been identified in Grove et al., 2019 as a gene that remained significant after Bonferroni correction following MAGMA gene-based association from the iPSYCH-PGC ASD meta analysis (P-value 1.63E-02). MSRA has been reported in several genome-wide meta-analyses as a candidate gene for schizophrenia (Goes et al., 2015; Li et al., 2017; Ikeda et al., 2018; Lam et al., 2019), while other association studies have identified MSRA as a candidate gene for bipolar disorder (Stahl et al., 2019), neuroticism (Fan et al., 2017; Nagel et al., 2018), and insomnia (Lane et al., 2019).
Molecular Function
This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity.
Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism
Discovery cohort: 7,699 SCZ cases and 18,327 controls of Chinese ancestry, 35,476 SCZ cases and 46,839 controls of European ancestry (PGC2). Replication cohort: 4,384 Chinese SCZ cases and 5,770 Chinese controls.
Discovery cohort of 14,023 SCZ cases and 31,505 controls of East Asian ancestry, replication cohort of 33,640 SCZ cases and 43,456 controls of European ancestry
Discovery cohort of 14,023 SCZ cases and 31,505 controls of East Asian ancestry, replication cohort of 33,640 SCZ cases and 43,456 controls of European ancestry
