Article
Genetics & Heredity
Minglong Cai, Tao Yuan, He Huang, Lan Gui, Li Zhang, Ziyuan Meng, Wenjuan Wu, Yujun Sheng, Xuejun Zhang
Summary: Vitiligo is a multifactorial polygenic disorder characterized by depigmented skin and hair. Genetic studies have identified new functional genes associated with vitiligo, as well as DNA methylation sites that are related to gene expression and disease risk. Colocalization analyses showed a shared genetic variant that alters DNA methylation and regulates gene expression, thereby influencing the risk of vitiligo.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Hao Lu, Luyu Ma, Cheng Quan, Lei Li, Yiming Lu, Gangqiao Zhou, Chenggang Zhang
Summary: This study introduces a computational framework called RegVar, based on deep neural networks, which accurately predicts the tissue-specific impact of non-coding regulatory variants on target genes. RegVar outperforms current methods in predicting regulatory variants and is capable of assessing the regulatory impact of any variant on its putative target genes in various tissues.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Genetics & Heredity
Margaret G. Guo, David L. Reynolds, Cheen E. Ang, Yingfei Liu, Yang Zhao, Laura K. H. Donohue, Zurab Siprashvili, Xue Yang, Yongjin Yoo, Smarajit Mondal, Audrey Hong, Jessica Kain, Lindsey Meservey, Tania Fabo, Ibtihal Elfaki, Laura N. Kellman, Nathan S. Abell, Yash Pershad, Vafa Bayat, Payam Etminani, Mark Holodniy, Daniel H. Geschwind, Stephen B. Montgomery, Laramie E. Duncan, Alexander E. Urban, Russ B. Altman, Marius Wernig, Paul A. Khavari
Summary: Noncoding variants play a role in the heritability of neuropsychiatric diseases. A study in developing human neural cells investigated 2,221 noncoding variants associated with ten neuropsychiatric disorders and identified differentially-active single-nucleotide variants (daSNVs) in specific neural cell types. Integrating epigenomic and transcriptomic data helped identify candidate disease-relevant target genes modulated by these daSNVs.
Article
Multidisciplinary Sciences
Giacomo Oliveira, Kari Stromhaug, Nicoletta Cieri, J. Bryan Iorgulescu, Susan Klaeger, Jacquelyn O. Wolff, Suzanna Rachimi, Vipheaviny Chea, Kate Krause, Samuel S. Freeman, Wandi Zhang, Shuqiang Li, David A. Braun, Donna Neuberg, Steven A. Carr, Kenneth J. Livak, Dennie T. Frederick, Edward F. Fritsch, Megan Wind-Rotolo, Nir Hacohen, Moshe Sade-Feldman, Charles H. Yoon, Derin B. Keskin, Patrick A. Ott, Scott J. Rodig, Genevieve M. Boland, Catherine J. Wu
Summary: In this study, the phenotype and tumor specificity of CD4 (+) T cells infiltrating human melanoma specimens were analyzed in depth, revealing that melanoma cells can directly induce exhausted cytotoxic CD4 (+) T cells through recognition of HLA class II-restricted neoantigens and HLA class I-restricted tumor-associated antigens. CD4 (+) T regulatory (T-Reg) cells can be indirectly elicited through the presentation of tumor antigens via antigen-presenting cells. Interestingly, a large number of tumor-reactive CD4 (+) T-Reg clones were stimulated directly by HLA class II-positive melanoma and showed specificity for melanoma neoantigens. These findings suggest that the presentation of HLA class II-restricted neoantigens and direct engagement of immunosuppressive CD4 (+) T-Reg cells are favored mechanisms of immune evasion in HLA class II-positive melanoma.
Article
Genetics & Heredity
Rui Chen, Zhihui Yang, Jiewei Liu, Xin Cai, Yongxia Huo, Zhijun Zhang, Ming Li, Hong Chang, Xiong-Jian Luo
Summary: The study identified 16 functional SNPs in 9 risk loci that disrupted the binding of 7 transcription factors, such as CTCF and REST. Potential target genes regulated by these functional SNPs in the human brain were identified through eQTL analysis. Dysregulation of target genes of the identified TF binding-disrupting SNPs was shown in BD patients compared with controls, and overexpression of PACS1 reduced dendritic spine density, revealing possible biological mechanisms of these functional SNPs in BD.
Article
Agronomy
Prabin Bajgain, James A. Anderson
Summary: The study genetically mapped six domestication traits of intermediate wheatgrass and identified markers and haplotype blocks significantly associated with these traits. Results suggest that increasing the frequency of favorable alleles in IWG populations via marker-assisted selection and genomic selection is an effective approach to improve IWG's domestication traits.
Article
Oncology
Dongyang Wang, Xiaohong Wu, Guanghui Jiang, Jianye Yang, Zhanhui Yu, Yanbo Yang, Wenqian Yang, Xiaohui Niu, Ke Tang, Jing Gong
Summary: Genome-wide association studies have identified thousands of SNPs associated with complex diseases and traits, but deciphering their functions remains challenging. Recent studies have shown that SNPs can alter chromatin accessibility, leading to differences in tumor susceptibility between individuals. Using caQTL analysis, we identified 9478 caQTLs in breast carcinoma that tend to alter transcription factor binding affinity and regulate open chromatin regions enriched in regulatory elements. Integration with eQTL data allowed us to identify caQTLs showing strong signals for colocalization with eQTLs, as well as caQTLs in GWAS loci. Survival analysis revealed that around 10% of caQTLs potentially influence patient prognosis. A user-friendly data portal, BCaQTL, was developed to provide easy access to relevant data. Our work facilitates the fine-mapping of regulatory mechanisms underlying cancer risk loci and the discovery of biomarkers or therapeutic targets for cancer prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Kirsty Ambridge, Ziying Ke, Julie C. Matte, Lara Bossini-Castillo, Joanna Kaplanis, Lucia Ramirez-Navarro, Anna Lorenc, Nikolina Nakic, Jorge Esparza-Gordillo, Wendy Rowan, David Wille, David F. Tough, Paola G. Bronson, Gosia Trynka
Summary: Single-cell RNA sequencing reveals dynamic regulation of gene expression during T cell activation, which may provide insights into the genetic susceptibility to immune diseases.
Article
Immunology
Vickram Tejwani, Amanda McCormack, Karthik Suresh, Han Woo, Ningchun Xu, Meghan F. Davis, Emily Brigham, Nadia N. Hansel, Meredith C. McCormack, Franco R. D'Alessio
Summary: In obese children with asthma, an increased expression of Ki-67 and FKBP51 in CD4(+) T-lymphocytes at baseline, as well as increased expression of FKBP51 after dexamethasone stimulation, was observed. However, these expressions showed no clear association with asthma control. Dexamethasone-induced CD4(+) FKBP51 expression was uniquely associated with worse asthma control in obese children with asthma, suggesting a potential mechanism for corticosteroid resistance in this population.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Clinical Neurology
Shiwu Li, Jiao Li, Jiewei Liu, Junyang Wang, Xiaoyan Li, Yongxia Huo, Yifan Li, Yixing Liu, Ming Li, Xiao Xiao, Xiong-Jian Luo
Summary: This study identified two functional variants at the 2q33.1 locus that disrupt the binding of CTCF, RAD21, and FOXP2, and found that they physically interact with the TYW5 gene and affect its expression. The study also demonstrated that TYW5 is upregulated in the brains of schizophrenia cases and showed its roles in neurodevelopment and dendritic spine formation. The association between one of the variants and schizophrenia was independently confirmed in a Chinese cohort.
Article
Genetics & Heredity
Edwin S. Iversen, Gary Lipton, Steven N. Hart, Kun Y. Lee, Chunling Hu, Eric C. Polley, Tina Pesaran, Amal Yussuf, Holly LaDuca, Elizabeth Chao, Rachid Karam, David E. Goldgar, Fergus J. Couch, Alvaro N. A. Monteiro
Summary: Loss-of-function variants in BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer. VarCall XT, a multifactorial approach, allows for the classification of these variants using multiple forms of genetic evidence, leading to more accurate assessment of cancer risk for patients.
NPJ GENOMIC MEDICINE
(2022)
Article
Biochemical Research Methods
Zhijian Li, Chao-Chung Kuo, Fabio Ticconi, Mina Shaigan, Julia Gehrmann, Eduardo Gade Gusmao, Manuel Allhoff, Martin Manolov, Martin Zenke, Ivan G. Costa
Summary: This article introduces the Regulatory Genomics Toolbox (RGT), a computational library for the integrative analysis of regulatory genomics data. RGT provides different functionalities to handle genomic signals and regions, and several tools have been developed for distinct downstream analyses. RGT facilitates the customization of computational methods to analyze specific regulatory genomics problems.
BMC BIOINFORMATICS
(2023)
Article
Medicine, General & Internal
Rui Chen, Jiewei Liu, Shiwu Li, Xiaoyan Li, Yongxia Huo, Yong-Gang Yao, Xiao Xiao, Ming Li, Xiong-Jian Luo
Summary: Through functional genomics study, we have systematically revealed the gene regulatory mechanisms of PD risk variants, generated the landscape of potential PD causal variants, and identified promising candidate genes for further functional characterization and drug development.
Article
Multidisciplinary Sciences
Atil Bisgin, Ozge Sonmezler, Ibrahim Boga, Mustafa Yilmaz
Summary: NGS of 103 CVID patients identified 112 different rare variants, with 49.1% classified as variants of uncertain significance and 1.8% classified as pathogenic. Rare variants in different genes were found to play a prominent role in disease susceptibility and etiology. However, the frequencies of these variants differed from population frequency databases.
SCIENTIFIC REPORTS
(2021)
Article
Plant Sciences
F. Taranto, S. Esposito, F. Fania, R. Sica, S. Marzario, G. Logozzo, T. Gioia, P. De Vita
Summary: The recent increase in genomic data for durum wheat has allowed for a better understanding of the effects of breeding on genetic structures and the identification of useful DNA markers for selection. In this study, 123 durum wheat accessions were evaluated for agronomic traits, and association mapping analysis revealed 28 QTNs related to plant morphology and kernel-related traits. The study also found strong associations for traits such as yellow berry and flowering time, providing valuable information for durum wheat breeding and genetics.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Statistics & Probability
Chris McKennan, Dan Nicolae
Summary: This article presents two methods, CBCV and CorrConf, for handling high-dimensional biological datasets with complex sample correlation structures. These methods demonstrate superior performance in choosing the number of latent confounding factors and estimating them, as evidenced by analysis of simulated and real data applications.
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
(2022)
Article
Respiratory System
Qi Yan, Erick Forno, Esther Herrera-Luis, Maria Pino-Yanes, Cancan Qi, Raimon Rios, Yueh-Ying Han, Soyeon Kim, Sam Oh, Edna Acosta-Perez, Rong Zhang, Donglei Hu, Celeste Eng, Scott Huntsman, Lydiana Avila, Nadia Boutaoui, Michelle M. Cloutier, Manuel E. Soto-Quiros, Cheng-Jian Xu, Scott T. Weiss, Jessica Lasky-Su, Megan R. Kiedrowski, Camila Figueiredo, Jennifer Bomberger, Mauricio L. Barreto, Glorisa Canino, Wei Chen, Gerard H. Koppelman, Esteban G. Burchard, Juan C. Celedon
Summary: In a GWAS meta-analysis of 4010 Latino youth with asthma, it was found that an SNP in the FLJ22447 gene was significantly associated with severe asthma exacerbations. This SNP was also linked to DNA methylation of a CpG site at the FLJ22447 locus, which was associated with increased expression of the KCINJ2-AS1 gene in nasal airway epithelium in Puerto Rican children and adolescents.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Critical Care Medicine
Brian Hallmark, Ganesa Wegienka, Suzanne Havstad, Dean Billheimer, Dennis Ownby, Eneida A. Mendonca, Lisa Gress, Debra A. Stern, Jocelyn Biagini Myers, Gurjit K. Khurana Hershey, Lori Hoepner, Rachel L. Miller, Robert F. Lemanske, Daniel J. Jackson, Diane R. Gold, George T. O'Connor, Dan L. Nicolae, James E. Gern, Carole Ober, Anne L. Wright, Fernando D. Martinez
Summary: This study explored the association between wheezing phenotypes and 17q12-21 genetic variants in children, revealing four latent classes of wheezing and highlighting the genetic locus as relevant to wheezing. Differences in genetic associations between European American and African American children were also observed, suggesting potential racial/ancestral influences on wheezing phenotypes.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Statistics & Probability
Matthew Reimherr, Xiao-Li Meng, Dan L. Nicolae
Summary: This paper presents a framework for quantifying the contribution of the prior to posterior inference in the presence of prior-likelihood discordance, expanding the classic notion of prior sample size in three directions. The framework is demonstrated using simulated and real data, showing the potential of quantifying the impact of a prior in specific inference problems. The discussion also touches upon conceptual and theoretical issues, such as the use of improper priors and priors with asymptotically non-vanishing influence.
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY
(2021)
Article
Allergy
Giselle S. Mosnaim, David A. Stempel, Candy Gonzalez, Brittney Adams, Naomi BenIsrael-Olive, Rahul Gondalia, Leanne Kaye, Madeleine Shalowitz, Stanley Szefler
Summary: This study found that patients tend to overestimate adherence to inhaled corticosteroids based on self-report, with significant discrepancies between self-report and objective data. Electronic medication monitors can provide clinicians with accurate information on medication adherence, leading to better management of asthma treatment.
Article
Biochemistry & Molecular Biology
Feng Guo, Yuan Hao, Li Zhang, Damien C. Croteau-Chonka, Derek Thibault, Parul Kothari, Lijia Li, Bruce D. Levy, Xiaobo Zhou, Benjamin A. Raby
Summary: GWAS-identified asthma susceptibility risk alleles increase the expression of ORMDL3, which promotes autophagy and cell death by impairing intracellular calcium mobilization through interacting with SERCA2, thereby impairing bronchial epithelial function in asthma.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Environmental Sciences
Minjian Chen, Yusheng Guan, Rui Huang, Jiawei Duan, Jingjing Zhou, Ting Chen, Xinru Wang, Yankai Xia, Stephanie J. London
Summary: This study investigated the relationship between the urinary exposome and metabolome during pregnancy and found many associations between chemical exposures and maternal metabolism. These associations may suggest a role of environmental modulation of maternal metabolome in the association between prenatal exposure and pregnancy and child health outcomes.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2022)
Article
Genetics & Heredity
Selene M. Clay, Nathan Schoettler, Andrew M. Goldstein, Peter Carbonetto, Matthew Dapas, Matthew C. Altman, Mario G. Rosasco, James E. Gern, Daniel J. Jackson, Hae Kyung Im, Matthew Stephens, Dan L. Nicolae, Carole Ober
Summary: This study investigates the association between asthma and variation in the human leukocyte antigen (HLA) complex. The results show shared and distinct causal variation in the HLA class I and class II regions for childhood-onset and adult-onset asthma. Gene expression levels and amino acid variation contribute to asthma risk. The study identifies potential causal variation and genes in the HLA region, with a focus on HLA-DQA2, HLA-DQB2, and HLA-DQA1*03:01 allele in adult-onset asthma.
Article
Biochemistry & Molecular Biology
Yura Lee, Han Chen, Wei Chen, Qibin Qi, Majid Afshar, Jianwen Cai, Martha L. Daviglus, Bharat Thyagarajan, Kari E. North, Stephanie J. London, Eric Boerwinkle, Juan C. Celedon, Robert C. Kaplan, Bing Yu
Summary: This study found a significant association between 1-arachidonoyl-GPA (20:4) and asthma, with stronger effects observed in women and individuals of Cuban and Puerto Rican backgrounds. Mutations in the FAD S2 gene affected the levels of 1-arachidonoyl-GPA (20:4), and genetically regulated high levels of 1-arachidonoyl-GPA (20:4) were associated with increased odds of asthma.
Article
Environmental Sciences
Julie D. White, Annah B. Wyss, Thanh T. Hoang, Mikyeong Lee, Marie Richards, Christine G. Parks, Laura E. Beane-Freeman, John L. Hankinson, David M. Umbach, Stephanie J. London
Summary: Frequent exposure to indoor wood burning was associated with lower pulmonary function among individuals with asthma. This group may need to reduce wood burning or consider using air filtration devices.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2022)
Article
Biochemistry & Molecular Biology
Lu Gong, Samuel Bates, Yujun Li, Xin Lin, Wenyi Wei, Xiaobo Zhou
Summary: Research found that SNPs within the FAM13A gene are significantly associated with chronic obstructive pulmonary disease and lung function. After treatment with cigarette smoke extract, FAM13A protein is phosphorylated at the serine 312 residue by AKT kinase and recognized by the CULLIN4A/DCAF1 E3 ligase complex, leading to its ubiquitination-mediated degradation. Additionally, AKT activation also leads to downregulation of FAM13A protein levels in mice with influenza or naphthalene-induced lung injury. Functionally, reduced FAM13A protein levels accelerate epithelial cell proliferation in murine lungs during the recovery phase after injury.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Pediatrics
Heather H. De Keyser, John T. Brinton, Samantha Bothwell, Megan Camacho, Allison Kempe, Stanley J. Szefler
Summary: This study aimed to test if a modest financial incentive improved medication adherence in adolescents with asthma. The results showed that giving adolescents a financial incentive did not significantly improve medication adherence. Therefore, further research is needed to determine effective interventions to optimize medication use in this group.
PEDIATRIC PULMONOLOGY
(2023)
Article
Genetics & Heredity
Nicolas Fragoso-Bargas, Christian M. Page, Bonnie R. Joubert, Stephanie J. London, Sindre Lee-Odegard, Julia O. Opsahl, Line Sletner, Anne K. Jenum, Elisabeth Qvigstad, Rashmi B. Prasad, Gunn-Helen Moen, Kare Birkeland, Christine Sommer
Summary: This research conducted an epigenome-wide association study on serum folate levels in maternal blood and identified CpG sites associated with folate levels. The findings provide new insights into the epigenomic component of serum folate levels.
Article
Pediatrics
Mariangela Soberon Felin, Kanix Wang, Catalina Raggi, Aliya Moreira, Abhinav Pandey, Andrew Grose, Zuleima Caballero, Claudia Rengifo-Herrera, Margarita Ramirez, Davina Moossazadeh, Catherine Castro, Jose Luis Sanchez Montalvo, Karen Leahy, Ying Zhou, Fatima Alibana Clouser, Maryam Siddiqui, Nicole Leong, Perpetua Goodall, Morgan Michalowski, Mahmoud Ismail, Monica Christmas, Stephen Schrantz, Ximena Norero, Dora Estripeaut, David Ellis, Kevin Ashi, Samantha Dovgin, Ashtyn Dixon, Xuan Li, Ian Begeman, Sharon Heichman, Joseph Lykins, Delba Villalobos-Cerrud, Lorena Fabrega, Connie Mendivil, Mario R. Quijada, Silvia Fernandez-Pirla, Valli de La Guardia, Digna Wong, Mayrene de LadronGuevara, Carlos Flores, Jovanna Borace, Anabel Garcia, Natividad Caballero, Maria Theresa Moreno de Saez, Michael Politis, Stephanie Ross, Mimansa Dogra, Vishan Dhamsania, Nicholas Graves, Marci Kirchberg, Kopal Mathur, Ashley Aue, Carlos M. Restrepo, Alejandro Llanes, German Guzman, Arturo Rebollon, Kenneth Boyer, Peter Heydemann, A. Gwendolyn Noble, Charles Swisher, Peter Rabiah, Shawn Withers, Teri Hull, Chunlei Su, Michael Blair, Paul Latkany, Ernest Mui, Daniel Vitor Vasconcelos-Santos, Alcibiades Villareal, Ambar Perez, Carlos Andres Naranjo Galvis, Monica Vargas Montes, Nestor Ivan Cardona Perez, Morgan Ramirez, Cy Chittenden, Edward Wang, Laura Lorena Garcia-Lopez, Juliana Munoz-Ortiz, Nicolas Rivera-Valdivia, Maria Cristina Bohorquez-Granados, Gabriela Castano de-la-Torre, Guillermo Padrieu, Juan David Valencia Hernandez, Daniel Celis-Giraldo, John Alejandro Acosta Davila, Elizabeth Torres, Manuela Mejia Oquendo, Jose Y. Arteaga-Rivera, Dan Nicolae, Andrey Rzhetsky, Nancy Roizen, Eileen Stillwaggon, Larry Sawers, Francois Peyron, Martine Wallon, Emanuelle Chapey, Pauline Levigne, Carmen Charter, Migdalia De Frias, Jose Montoya, Cindy Press, Raymund Ramirez, Despina Contopoulos-Ioannidis, Yvonne Maldonado, Oliver Liesenfeld, Carlos Gomez, Kelsey Wheeler, Ellen Holfels, David Frim, David McLone, Richard Penn, William Cohen, Samantha Zehar, James McAuley, Denis Limonne, Sandrine Houze, Sylvie Abraham, Raphael Piarroux, Vera Tesic, Kathleen Beavis, Ana Abeleda, Mari Sautter, Bouchra El Mansouri, Adlaoui El Bachir, Fatima Amarir, Kamal El Bissati, Alejandra de-la-Torre, Gabrielle Britton, Jorge Motta, Eduardo Ortega-Barria, Isabel Luz Romero, Paul Meier, Michael Grigg, Jorge Gomez-Marin, Jagannatha Rao Kosagisharaf, Xavier Saez Llorens, Osvaldo Reyes, Rima McLeod
Summary: This review examines the rates of toxoplasmosis in Panama and Colombia, and explores the relationship between the infection rates and factors such as poverty and proximity to water sources. The study utilizes screening maps, seroprevalence maps, and risk factor mathematical models to identify regions that would benefit from comprehensive, preventive healthcare campaigns.
CURRENT PEDIATRICS REPORTS
(2022)
Article
Medicine, Research & Experimental
Patrick H. Ryan, Cole Brokamp, Jeff Blossom, Nathan Lothrop, Rachel L. Miller, Paloma Beamer, Cynthia M. Visness, Antonella Zanobetti, Howard Andrews, Leonard B. Bacharier, Tina Hartert, Christine C. Johnson, Dennis Ownby, Robert F. Lemanske, Heike Gibson, Weeberb Requia, Brent Coull, Edward M. Zoratti, Anne L. Wright, Fernando D. Martinez, Christine M. Seroogy, James E. Gern, Diane R. Gold
Summary: This study presents a standardized and reproducible method for conducting geospatial analyses in multisite studies. By utilizing census tract-level information and collaborative efforts among cohorts located throughout the USA, the feasibility of geospatial analyses across multiple study sites was demonstrated.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
