Article
Biotechnology & Applied Microbiology
Zhichi Zeng, Sichen Zhang, Wenyan Li, Baoshan Chen, Wenlan Li
Summary: This study investigated the molecular mechanism of cold tolerance in rice through transcriptome analysis. It found that hormone-mediated defense response plays an important role in protecting rice plants from physiological damage under low-temperature stress. The study also provided a potential regulatory mechanism for the cold stress and recovery of rice cultivars and identified candidate central genes.
Article
Environmental Sciences
Jing Wu, Dongfang Wang, Lailai Yan, Meixiang Jia, Jishui Zhang, Songping Han, Jisheng Han, Jingyu Wang, Xi Chen, Rong Zhang
Summary: This case-control study explored the associations between autism spectrum disorder (ASD) and serum concentrations of nine chemical elements in children. The study found that the concentrations of certain elements were associated with the risk and severity of ASD.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Psychiatry
Zhen-Qing Zhang, Wei-Wei Wu, Jin-Dong Chen, Guang-Yin Zhang, Jing-Yu Lin, Yan-Kun Wu, Yu Zhang, Yun-Ai Su, Ji-Tao Li, Tian-Mei Si
Summary: This study identified candidate pathways and genes involved in the pathogenesis of bipolar disorder (BD) using methods such as weighted gene coexpression network analysis (WGCNA). Hub genes like NOTCH1 were highlighted, along with biological processes and pathways like actin filament-based process and MAPK signaling. These findings provide new insights for the diagnosis and treatment of BD.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Chuanchuan Wang, Weixuan Chen, Yishan Jiang, Xiao Xiao, Qianhui Zou, Jiarui Liang, Yu Zhao, Qianxu Wang, Tian Yuan, Rui Guo, Xuebo Liu, Zhigang Liu
Summary: Autism Spectrum Disorder (ASD) symptoms may be improved through modulation of gut microbiota. This study investigated the effects of a synbiotic treatment on an ASD-like mouse model, and found that it rectified social impairments, attenuated inflammatory cytokine expressions, protected gut barrier integrity, and altered gut microbiota composition. The synbiotic treatment elevated beneficial metabolites and upregulated genes associated with their synthesis. Overall, the synbiotic combination mitigated ASD-related social impairments through regulation of the gut-brain axis.
Article
Genetics & Heredity
Michael Wainberg, Roarke A. Kamber, Akshay Balsubramani, Robin M. Meyers, Nasa Sinnott-Armstrong, Daniel Hornburg, Lihua Jiang, Joanne Chan, Ruiqi Jian, Mingxin Gu, Anna Shcherbina, Michael M. Dubreuil, Kaitlyn Spees, Wouter Meuleman, Michael P. Snyder, Michael C. Bassik, Anshul Kundaje
Summary: A new statistical method has been developed to robustly identify gene co-essentiality and yield a genome-wide set of functional modules, predicting the functions of 108 uncharacterized genes effectively.
Article
Oncology
Mingrui Zhu, Jiwoong Kim, Qing Deng, Biagio Ricciuti, Joao V. Alessi, Buse Eglenen-Polat, Matthew E. Bender, Hai-Cheng Huang, Ryan R. Kowash, Ileana Cuevas, Zachary T. Bennett, Jinming Gao, John D. Minna, Diego H. Castrillon, Mark M. Awad, Lin Xu, Esra A. Akbay
Summary: The role of tumor mutational burden (TMB) in tumor immunity is important. Expressing a hypermutated DNA polymerase E variant in lung epithelial cells increases TMB in a mouse model of lung cancer. The association between Pole mutation and p53 affects immunogenicity and sensitivity to immune checkpoint blockade. TP53 truncating mutations in lung tumors are associated with lower survival rates in immunotherapy.
Article
Behavioral Sciences
Jacqueline N. Crawley
Summary: More than 100 single gene mutations and copy number variants have been identified as risk factors for autism spectrum disorder. By introducing similar mutations into the genomes of laboratory mice and other species, researchers have been able to understand how each mutation contributes to the development of autism symptoms. Using behavioral assays that mirror the diagnostic criteria for autism, scientists have discovered the behavioral consequences of these mutations in animal models. These findings, along with other measures such as electrophysiology and neuroanatomy, are being used to develop effective therapeutic interventions in translational investigations.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Psychiatry
Liangyu Kang, Jue Liu, Yan Liu, Wannian Liang, Fude Yang, Min Liu
Summary: This study aimed to estimate the burden trend of autism spectrum disorder (ASD) at global, regional, and national levels from 1990 to 2019. Data on incident cases, incidence rates, prevalent cases, prevalence rates, disability-adjusted life years (DALYs), and DALY rates of ASD among children under 5 years were collected. The temporal trends of ASD burden were analyzed through calculating the percentage of relative changes in cases and the estimated annual percentage changes (EAPCs) of rates. Pearson correlation analysis was conducted to explore the influential factors for EAPC.
ASIAN JOURNAL OF PSYCHIATRY
(2023)
Article
Genetics & Heredity
Marc Woodbury-Smith, Sylvia Lamoureux, Ghausia Begum, Nasna Nassir, Hosneara Akter, Darren D. O'Rielly, Proton Rahman, Richard F. Wintle, Stephen W. Scherer, Mohammed Uddin
Summary: This study conducted whole exome sequencing on ASD brain tissue samples and identified a small number of rare post-zygotic mutations and germline mutations in key ASD genes. The establishment of tissue resources available to the scientific community will facilitate the discovery of new mutations for ASD and other neurodevelopmental disorders.
Article
Cardiac & Cardiovascular Systems
Weikang Bian, Zhicheng Wang, Xiaobo Li, Xiao-Xin Jiang, Hongsong Zhang, Zhizhong Liu, Dai-Min Zhang
Summary: In this study, weighted gene coexpression network analysis (WGCNA) was used to identify the key module and hub genes for heart failure (HF). Differential gene expression analysis, coexpression network construction, functional enrichment analysis, and protein-protein interaction network construction were conducted to identify potential hub genes. The results may provide potential biomarkers for the diagnosis of HF and enhance our understanding of the molecular mechanisms underlying HF.
Article
Genetics & Heredity
Shuangkuai Wang, Yuantao Tong, Hui Zong, Xuewen Xu, M. James C. Crabbe, Ying Wang, Xiaoyan Zhang
Summary: Tumor mutational burden (TMB) is a potential biomarker for predicting the response and effect of immune checkpoint inhibitors (ICIs). In this study, a text-mining technology was applied to construct specific TMB-associated gene panels across various cancer types. The correlation between TMB genes and immune cell infiltrating in colorectal cancer was further analyzed. The results showed that the TMB gene panels performed well and TMB differentially expressed genes (DEGs) showed great potential value in immune cell infiltration and in predicting survival.
Article
Immunology
Yi Luo, Keyi Lv, Zhulin Du, Dandan Zhang, Mei Chen, Jing Luo, Lian Wang, Tianyao Liu, Hong Gong, Xiaotang Fan
Summary: Autism spectrum disorder (ASD) lacks effective pharmacological treatments. Minocycline, known for its anti-inflammatory properties and neuroprotective effects, inhibits microglial activation. This study used a mouse model of autism and found that minocycline administration improved ASD-like behaviors, neurogenesis, and inhibited microglia activation. These findings suggest that minocycline supplementation might be a potential strategy for improving ASD symptoms.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Editorial Material
Behavioral Sciences
Alison Singer, Amy Lutz, Jill Escher, Alycia Halladay
Summary: There have been suggestions to limit certain words used to describe autism, but these limitations have resulted in negative consequences. Scientists and clinicians should be able to use appropriate vocabulary to describe and support autistic individuals without fear of censorship or retribution.
Article
Biochemistry & Molecular Biology
Regina Putri Virgirinia, Makoto Nakamura, Kimiko Takebayashi-Suzuki, Fatchiyah Fatchiyah, Atsushi Suzuki
Summary: In addition to Clk2, Clk1 and Clk3 also play a role in the formation of neural tissue in Xenopus. Clk3 is essential for promoting neural development during early embryogenesis in Xenopus.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Laura P. Stabile, Vinod Kumar, Autumn Gaither-Davis, Eric H. Huang, Frank P. Vendetti, Princey Devadassan, Sanja Dacic, Riyue Bao, Richard A. Steinman, Timothy F. Burns, Christopher J. Bakkenist
Summary: The establishment of a tobacco-associated murine LUAD cell line FVBW-17 provides a valuable preclinical model for studying lung cancer biology and testing novel therapies, including immune-based treatments such as anti-PD-L1 therapy.
Article
Cell Biology
Xiangchen Gu, Hongliu Yang, Xin Sheng, Yi-An Ko, Chengxiang Qiu, Jihwan Park, Shizheng Huang, Rachel Kember, Renae L. Judy, Joseph Park, Scott M. Damrauer, Girish Nadkarni, Ruth J. F. Loos, Vy Thi Ha My, Kumardeep Chaudhary, Erwin P. Bottinger, Ishan Paranjpe, Aparna Saha, Christopher Brown, Shreeram Akilesh, Adriana M. Hung, Matthew Palmer, Aris Baras, John D. Overton, Jeffrey Reid, Marylyn Ritchie, Daniel J. Rader, Katalin Susztak
Summary: The study identified a potential correlation between low expression of MANBA in the kidneys of individuals with CKD risk genotype and an increased incidence of renal failure in individuals with rare loss-of-function coding variants in MANBA. The findings highlight the importance of the MANBA gene in kidney health, as it is highly expressed in human kidney tubule cells and appears to play a role in kidney disease development.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemical Research Methods
Kelly Finke, Michael Kourakos, Gabriela Brown, Huyen Trang Dang, Shi Jie Samuel Tan, Yuval B. Simons, Shweta Ramdas, Alejandro A. Schaeffer, Rachel L. Kember, Maja Bucan, Sara Mathieson
Summary: This study introduces a novel algorithm for reconstructing ancestral genomes in order to track the transmission of haplotypes over generations and understand the genetic basis of diseases segregating in extended families. The algorithm can handle complex pedigree structures and enable the reconstruction of ancestral genomes in large family pedigrees.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Substance Abuse
Cecilia Dao, Hang Zhou, Aeron Small, Kirsha S. Gordon, Boyang Li, Rachel L. Kember, Yixuan Ye, Joel Gelernter, Ke Xu, Henry R. Kranzler, Hongyu Zhao, Amy C. Justice
Summary: By differentiating between former drinkers and lifelong abstainers, the study aimed to improve the genome-wide association results of the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Removing former drinkers resulted in a stronger association with a specific polymorphism, more significant SNPs, and genomic loci. There were significant differences in polygenic risk scores for related diseases between former drinkers and lifelong abstainers.
Article
Psychology, Clinical
Emma C. Johnson, Manav Kapoor, Alexander S. Hatoum, Hang Zhou, Renato Polimanti, Frank R. Wendt, Raymond K. Walters, Dongbing Lai, Rachel L. Kember, Sarah Hartz, Jacquelyn L. Meyers, Roseann E. Peterson, Stephan Ripke, Tim B. Bigdeli, Ayman H. Fanous, Carlos N. Pato, Michele T. Pato, Alison M. Goate, Henry R. Kranzler, Michael C. O'Donovan, James T. R. Walters, Joel Gelernter, Howard J. Edenberg, Arpana Agrawal
Summary: This study used large-scale genome-wide association study data to identify genetic correlations between alcohol use disorder and schizophrenia, as well as shared and disorder-specific genetic variants. The study also found evidence of gene expression mediation in the prefrontal cortex for genes associated with both disorders.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Emily E. Hartwell, Alison K. Merikangas, Shefali S. Verma, Marylyn D. Ritchie, Henry R. Kranzler, Rachel L. Kember
Summary: This study investigated the relationship between SUD PRS and primary phenotypes, finding associations but not diagnostic predictability. PheWAS analysis revealed cross-trait associations in psychiatric disorders and medical conditions.
Editorial Material
Psychiatry
Henry R. Kranzler, Hang Zhou, Rachel L. Kember
AMERICAN JOURNAL OF PSYCHIATRY
(2022)
Article
Substance Abuse
Richard C. Crist, Rachel Vickers-Smith, Rachel L. Kember, Christopher T. Rentsch, Heng Xu, E. Jennifer Edelman, Emily E. Hartwell, Kyle M. Kampman, Henry R. Kranzler
Summary: This study conducted a genome-wide association study (GWAS) of buprenorphine treatment response in European-ancestry individuals, identifying six nominally significant loci. Factors associated with reduced odds of buprenorphine response included higher daily dosage, more urine drug screens, and history of hepatitis C infection, while older age was associated with increased odds of response.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Article
Genetics & Heredity
Catherine Tcheandjieu, Ke Xiao, Helio Tejeda, Julie A. Lynch, Sanni Ruotsalainen, Tiffany Bellomo, Madhuri Palnati, Renae Judy, Derek Klarin, Rachel L. Kember, Shefali Verma, Aarno Palotie, Mark Daly, Marylyn Ritchie, Daniel J. Rader, Manuel A. Rivas, Philip Tsao, Scott Damrauer, James R. Priest
Summary: This study used automated extraction of ascending aortic diameter from cardiac magnetic resonance images and conducted a genome-wide association study. The polygenic score constructed from multiple loci was able to predict the risk of thoracic aortic aneurysm in different populations. Additionally, the study revealed the causal role of blood pressure in reducing aortic dilation.
Article
Neurosciences
Tiffany Love, Andrey A. Shabalin, Rachel L. Kember, Anna R. Docherty, Hang Zhou, Vincent Koppelmans, Joel Gelernter, Anne K. Baker, Emily Hartwell, Jacob Dubroff, Jon-Kar Zubieta, Henry R. Kranzler
Summary: This study found a link between polygenic risk for major depressive disorder (MDD) and opioid use disorder (OUD) and opioid system activity, particularly under stress. The association was most significant among females and may help explain the high comorbidity between MDD and OUD. The results also suggest that opioid-modulating interventions may be useful in treating MDD and OUD.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Sylvanus Toikumo, Heng Xu, Joel Gelernter, Rachel L. Kember, Henry R. Kranzler
Summary: This study identified genes associated with substance use traits and investigated their impact on protein abundance and transcript levels in the brain. The findings suggest that these genes may play a role in the genetic risk for substance use disorders and could serve as potential targets for medication development and biomarkers.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Rachel L. Kember, Emily E. Hartwell, Heng Xu, James Rotenberg, Laura Almasy, Hang Zhou, Joel Gelernter, Henry R. Kranzler
Summary: The study found that genetic pleiotropy is a factor in the co-occurrence of substance use disorders (SUDs) with other psychiatric disorders and SUDs. Polygenic risk scores were used to evaluate the genetic pleiotropic effects of 4 major substance-related traits. The results showed that in individuals of African ancestry, genetic risk scores for SUDs were associated with their respective primary DSM diagnoses, while in individuals of European ancestry, genetic risk scores for SUDs were associated with multiple substance-related phenotypes.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Rachel L. Kember, Rachel Vickers-Smith, Heng Xu, Sylvanus Toikumo, Maria Niarchou, Hang Zhou, Emily E. Hartwell, Richard C. Crist, Christopher T. Rentsch, Lea K. Davis, Amy C. Justice, Sandra Sanchez-Roige, Kyle M. Kampman, Joel Gelernter, Henry R. Kranzler
Summary: This study conducted a meta-analysis to identify genetic loci associated with opioid use disorder (OUD). The analysis revealed 14 loci, of which 12 were novel. The study also found significant genetic correlations between OUD and psychiatric disorders as well as other substance use-related traits. Furthermore, the findings suggest that OUD is a brain disease, providing important insights for reducing stigma and addressing the opioid epidemic.
NATURE NEUROSCIENCE
(2022)
Article
Health Care Sciences & Services
Anurag Verma, Scott M. Damrauer, Nawar Naseer, JoEllen Weaver, Colleen M. Kripke, Lindsay Guare, Giorgio Sirugo, Rachel L. Kember, Theodore G. Drivas, Scott M. Dudek, Yuki Bradford, Anastasia Lucas, Renae Judy, Shefali S. Verma, Emma Meagher, Katherine L. Nathanson, Michael Feldman, Marylyn D. Ritchie, Daniel J. Rader
Summary: The Penn Medicine BioBank is an EHR-linked biobank that integrates a variety of health information with genomic data, making it one of the most diverse medical biobanks. Its significance lies in expanding diversity in genetic and translational research, and its potential for biological discovery and precision medicine.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Elizabeth M. Humphries, Kwangmi Ahn, Rachel L. Kember, Fabiana L. Lopes, Evelina Mocci, Juan M. Peralta, John Blangero, David C. Glahn, Fernando S. Goes, Peter P. Zandi, Peter Kochunov, Cristopher Van Hout, Alan R. Shuldiner, Toni I. Pollin, Braxton D. Mitchell, Maja Bucan, L. Elliot Hong, Francis J. McMahon, Seth A. Ament
Summary: By conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish, four significant risk loci were identified, all of which were associated with more than a 2-fold relative risk. Further assessments revealed effects of these risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that these risk loci may harbor novel risk-associated genes, which interact with known neuropsychiatry-associated genes through gene interaction networks. Annotation of the variants at these risk loci revealed enrichment of non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. These findings provide valuable insights into the genetic architecture of mood disorders and serve as a foundation for mechanistic and clinical studies.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Youshu Cheng, Cecilia Dao, Hang Zhou, Boyang Li, Rachel L. Kember, Sylvanus Toikumo, Hongyu Zhao, Joel Gelernter, Henry R. Kranzler, Amy C. Justice, Ke Xu
Summary: Smoking behaviors and alcohol use disorder commonly co-occur and are moderately heritable. Previous single-trait GWAS studies have identified multiple loci for smoking and AUD. However, limited by small samples, GWASs aiming to identify loci contributing to co-occurring smoking and AUD have been less informative. Using multi-trait analysis of GWASs (MTAG) with data from the Million Veteran Program, this study identified novel loci associated with smoking initiation and cessation. Functional annotation highlighted biologically important regions contributing to smoking behaviors. MTAG results did not enhance discovery for smoking behaviors and alcohol consumption compared to single-trait GWAS. This study provides new insights into the pleiotropic effects of genetic variants on smoking behavior and AUD through the application of MTAG.
TRANSLATIONAL PSYCHIATRY
(2023)