Prioritization of schizophrenia risk genes from GWAS results by integrating multi-omics data

Schizophrenia (SCZ) is a polygenic disease with a heritability approaching 80%. Over 100 SCZ-related loci have so far been identified by genome-wide association studies (GWAS). However, the risk genes associated with these loci often remain unknown. We present a new risk gene predictor, rGAT-omics, that integrates multi-omics data under a Bayesian framework by combining the Hotelling and Box–Cox transformations. The Bayesian framework was constructed using gene ontology, tissue-specific protein–protein networks, and multi-omics data including differentially expressed genes in SCZ and controls, distance from genes to the index single-nucleotide polymorphisms (SNPs), and de novo mutations. The application of rGAT-omics to the 108 loci identified by a recent GWAS study of SCZ predicted 103 high-risk genes (HRGs) that explain a high proportion of SCZ heritability (Enrichment = 43.44 and p=9.30×10−9). HRGs were shown to be significantly (padj=5.35×10−7) enriched in genes associated with neurological activities, and more likely to be expressed in brain tissues and SCZ-associated cell types than background genes. The predicted HRGs included 16 novel genes not present in any existing databases of SCZ-associated genes or previously predicted to be SCZ risk genes by any other method. More importantly, 13 of these 16 genes were not the nearest to the index SNP markers, and them would have been difficult to identify as risk genes by conventional approaches while ten out of the 16 genes are associated with neurological functions that make them prime candidates for pathological involvement in SCZ. Therefore, rGAT-omics has revealed novel insights into the molecular mechanisms underlying SCZ and could provide potential clues to future therapies

Distinct sequence features underlie microdeletions and gross deletions in the human genome

Microdeletions and gross deletions are important causes (~20%) of human inherited disease and their genomic locations are strongly influenced by the local DNA sequence environment. This notwithstanding, no study has systematically examined their underlying generative mechanisms. Here, we obtained 42,098 pathogenic microdeletions and gross deletions from the Human Gene Mutation Database (HGMD) that together form a continuum of germline deletions ranging in size from 1bp to 28,394,429bp. We analyzed the DNA sequence within 1-kb of the breakpoint junctions and found that the frequencies of non-B DNA-forming repeats, GC-content, and the presence of seven of 78 specific sequence motifs in the vicinity of pathogenic deletions correlated with deletion length for deletions of length ≤30 bp. Further, we found that the presence of DR, GQ and STR repeats is important for the formation of longer deletions (>30 bp) but not for the formation of shorter deletions (≤30 bp) whilst significantly (Chi-square test P-value30 bp). We provide evidence to support a functional distinction between microdeletions and gross deletions. Finally, we propose that a deletion length cut-off of 25-30bp may serve as an objective means to functionally distinguish microdeletions from gross deletions

Regulatory controls of duplicated gene expression during fiber development in allotetraploid cotton.

Polyploidy complicates transcriptional regulation and increases phenotypic diversity in organisms. The dynamics of genetic regulation of gene expression between coresident subgenomes in polyploids remains to be understood. Here we document the genetic regulation of fiber development in allotetraploid cotton Gossypium hirsutum by sequencing 376 genomes and 2,215 time-series transcriptomes. We characterize 1,258 genes comprising 36 genetic modules that control staged fiber development and uncover genetic components governing their partitioned expression relative to subgenomic duplicated genes (homoeologs). Only about 30% of fiber quality-related homoeologs show phenotypically favorable allele aggregation in cultivars, highlighting the potential for subgenome additivity in fiber improvement. We envision a genome-enabled breeding strategy, with particular attention to 48 favorable alleles related to fiber phenotypes that have been subjected to purifying selection during domestication. Our work delineates the dynamics of gene regulation during fiber development and highlights the potential of subgenomic coordination underpinning phenotypes in polyploid plants. [Abstract copyright: © 2023. The Author(s).

The Impacts of Gasoline Stations on Residential Property Values: A Case Study in Xuancheng, China

In this paper, we examine the effect of gasoline stations on residential multifamily housing prices in Xuancheng, China. First, a survey examining beliefs and the Not in My Backyard (NIMBY) issues associated with gasoline stations investigated the public attitude toward the impact of gasoline stations. The results show that, although the gasoline stations have adopted advanced safety management, 86% of people believe that they will decrease nearby housing prices. Second, in March and April 2016, a hedonic pricing model was used to measure the impact of gas stations on the sales' prices of 601 residential units in 22 multifamily neighborhoods that are up to 1,000 meters from the gas stations. The results show that housing prices increase significantly with every additional kilometer from the nearest gasoline station, and the closer to the gasoline station that the house is, the more negative the impact on the housing price. The closest 100-meter band showed almost a 16% reduction in housing price, and the furthest affected band (301–600 meters) was down by almost 9%. The negative effect was not observed at distances beyond 600 meters

Inferring the genetic relationship between brain imaging-derived phenotypes and risk of complex diseases by Mendelian randomization and genome-wide colocalization

Observational studies consistently disclose brain imaging-derived phenotypes (IDPs) as critical markers for early diagnosis of both brain disorders and cardiovascular diseases. However, it remains unclear about the shared genetic landscape between brain IDPs and the risk of brain disorders and cardiovascular diseases, restricting the applications of potential diagnostic techniques through brain IDPs. Here, we reported genetic correlations and putative causal relationships between 921 brain IDPs, 20 brain disorders and six cardiovascular diseases by leveraging their large-scale genome-wide association study (GWAS) summary statistics. Applications of Mendelian randomization (MR) identified significant putative causal effects of multiple region-specific brain IDPs in relation to the increased risks for amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), autism spectrum disorder (ASD) and schizophrenia (SCZ). We also found brain IDPs specifically from temporal lobe as a putatively causal consequence of hypertension. The genome-wide colocalization analysis identified three genomic regions in which MDD, ASD and SCZ colocalized with the brain IDPs, and two novel SNPs to be associated with ASD, SCZ, and multiple brain IDPs. Furthermore, we identified a list of candidate genes involved in the shared genetics underlying pairs of brain IDPs and MDD, ASD, SCZ, ALS and hypertension. Our results provide novel insights into the genetic relationships between brain disorders and cardiovascular diseases and brain IDP, which may server as clues for using brain IDPs to predict risks of diseases

High Verdet Constant Glass for Magnetic Field Sensors

Due to the high transparency, high Verdet constant, as well as easy processing properties, rare-earth ion-doped glasses have demonstrated great potential in magneto-optical (MO) applications. However, the variation in the valence state of rare-earth ions (Tb3+ to Tb4+) resulted in the decreased effective concentration of the paramagnetic ions and thus degraded MO performance. Here, a strategy was proposed to inhibit the oxidation of Tb3+ into Tb4+ as well as improve the thermal stability by tuning the optical basicity of glass networks. Moreover, the depolymerization of the glass network was modulated to accommodate more Tb ions. Thus, a record high effective concentration (14.19 × 1021/cm3) of Tb ions in glass was achieved, generating a high Verdet constant of 113 rad/(T·m) at 650 nm. Lastly, the first application of MO glass for magnetic field sensors was demonstrated, achieving a sensitivity of 0.139 rad/T. We hope our work provides guidance for the fabrication of MO glass with high performance and thermal stability and could push MO glass one step further for magnetic sensing applications