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Catalytically active structure of Mevalonate kinase in complex with the ATP and the mevalonate substrate.

Numerous developmental genes have been linked to schizophrenia (SZ) by case-control and genome-wide association studies, suggesting that neurodevelopmental disturbances are major pathogenic mechanisms. However, no neurodevelopmental deficit has been definitively linked to SZ occurrence, likely due to disease heterogeneity and the differential effects of various gene variants across ethnicities. Hence, it is critical to examine linkages in specific ethnic populations, such as Han Chinese. The newly identified RhoGAP ARHGAP18 is likely involved in neurodevelopment through regulation of RhoA/C. Here we describe four single nucleotide polymorphisms (SNPs) in ARHGAP18 associated with SZ across a cohort of >2000 cases and controls from the Han population. Two SNPs, rs7758025 and rs9483050, displayed significant differences between case and control groups both in genotype (P = 0.0002 and P = 7.54×10−6) and allelic frequencies (P = 4.36×10−5 and P = 5.98×10−7), respectively. The AG haplotype in rs7758025−rs9385502 was strongly associated with the occurrence of SZ (P = 0.0012, OR = 0.67, 95% CI = 0.48–0.93), an association that still held following a 1000-times random permutation test (P = 0.022). In an independently collected validation cohort, rs9483050 was the SNP most strongly associated with SZ. In addition, the allelic frequencies of rs12197901 remained associated with SZ in the combined cohort (P = 0.021), although not in the validation cohort alone (P = 0.251). Collectively, our data suggest the ARHGAP18 may confer vulnerability to SZ in the Chinese Han population, providing additional evidence for the involvement of neurodevelopmental dysfunction in the pathogenesis of schizophrenia.

The above article, published online on 4 April 2023 in Wiley Online Library (wileyonlinelibrary.com) as an Accepted Article (https://doi.org/10.1002/2211‐5463.13606) has been withdrawn by agreement between the authors, the journal Editor‐in‐Chief Miguel A. De la Rosa, and John Wiley and Sons. The withdrawal has been agreed due to a dispute over authorship and the conceptualization of some of the data.

Adipose tissue is a major component for the regulation of energy homeostasis by storage and release of lipids. As a core element of RNA-induced silencing complex, Ago2 plays critical role in maintenance of systemic metabolic demand. Here we show that high-fat diet feeding mice exhibited an increase in body mass alongside systematic insulin resistance and altered rate of energy expenditure. Interestingly, Ago2 expression is associated with obesity and increased in adipose tissues. Moreover, increase of Ago2 inhibited the expression of AMPKα by promoting its targeting by miR-148a, the most abundant microRNA in the adipose tissues. Those results suggested that Ago2-miR-148a-AMPKα signaling pathway play an important function in the developing obesity and adiposity and will further provide basic research data for the potential clinic treatment of obesity.

Adipose tissue is a major component for the regulation of energy homeostasis by storage and release of lipids. As a core element of RNA-induced silencing complex, Ago2 plays critical role in maintenance of systemic metabolic demand. Here we show that high-fat diet feeding mice exhibited an increase in body mass alongside systematic insulin resistance and altered rate of energy expenditure. Interestingly, Ago2 expression is associated with obesity and increased in adipose tissues. Moreover, increase of Ago2 inhibited the expression of AMPKα by promoting its targeting by miR-148a, the most abundant microRNA in the adipose tissues. Those results suggested that Ago2-miR-148a-AMPKα signaling pathway play an important function in the developing obesity and adiposity and will further provide basic research data for the potential clinic treatment of obesity.

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