Editorial Material
Medicine, General & Internal
Lisa Bastarache, Joshua C. Denny, Dan M. Roden
Summary: This article discusses the concept and methodology of phenome-wide association studies, which aim to identify associations between genetic variations and phenotypic traits using a dataset.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Xiaoyu Liang, Xuewei Cao, Qiuying Sha, Shuanglin Zhang
Summary: The article introduces a novel multivariate method for phenome-wide association studies (PheWAS) and demonstrates its superiority through extensive simulation studies and real-life application. The proposed method involves hierarchical clustering, clustering linear combination, and false discovery rate control steps.
Review
Genetics & Heredity
Shiying Liu, Dana C. Crawford
Summary: Phenome-wide association studies (PheWAS) have significantly advanced in the past decade, uncovering novel genotype-phenotype relationships. With advancements in methods and resources, the potential of PheWAS has been realized to a greater extent, but challenges remain in further understanding the complex genetic architecture underlying human diseases and traits.
TRENDS IN GENETICS
(2022)
Article
Biochemical Research Methods
Richard J. Packer, Alex T. Williams, William Hennah, Micaela T. Eisenberg, Nick Shrine, Katherine A. Fawcett, Willow Pearson, Anna L. Guyatt, Ahmed Edris, Edward J. Hollox, Mikko Marttila, Balasubramanya S. Rao, John Raymond Bratty, Louise Wain, Frank Dudbridge, Martin D. Tobin
Summary: DeepPheWAS is an R package that allows for phenome-wide association studies by creating curated composite phenotypes and integrating quantitative phenotypes from primary care data, as well as disease progression and drug response phenotypes. It provides tools for efficient analysis of associations with genetic input under any genetic model, including optional sex-stratified analysis and phenotype development.
Article
Genetics & Heredity
J. Lucas Boatwright, Sirjan Sapkota, Stephen Kresovich
Summary: High-throughput genomics and phenomics have improved the ability to detect genotype-to-phenotype associations in plants. However, determining the functional effects of associated genes/loci remains challenging and expensive. In this study, we used phenomic imputation and a Bayesian Genome-Phenome Wide Association Study (BGPWAS) model to identify putative loss-of-function effects in a maize dataset. Our approach facilitated the identification of loss-of-function alleles and their effects on protein structure and folding, providing valuable insights for precision genomics and breeding.
FRONTIERS IN GENETICS
(2023)
Article
Biochemical Research Methods
Itziar Irigoien, Bru Cormand, Maria Soler-Artigas, Cristina Sanchez-Mora, Josep-Antoni Ramos-Quiroga, Concepcion Arenas
Summary: With the rise of GWAS, the analysis of large-scale SNP data has become crucial in biomedical research. This paper proposes a new method based on genetic distances between individuals to identify disease-related SNPs in case-control studies. By considering population substructure and avoiding multiple testing issues, the method provides ordered lists of SNPs and serves as a useful tool for researchers to focus their attention in the initial stage.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Editorial Material
Genetics & Heredity
Gerard G. Dumancas, Destiny Harrison, Jonathan Adam Rico, Pia Regina Fatima C. Zamora, Aretha G. Liwag, Joselito F. Villaruz, Ma. Luz Vicenta V. Guanzon, Hans Francis D. Ferraris, Patrick Joseph B. Jalandoni, Webster F. Padernal, Bea Nestie L. Villareal, Ria A. Maculada, Rachael Mae A. Fernandez, Felix Ray Villa, Romulo de Castro
Summary: Despite the demand for PheWAS in developing countries, limitations related to resources and practicality may pose challenges.
TRENDS IN GENETICS
(2022)
Review
Genetics & Heredity
Lijuan Wang, Xiaomeng Zhang, Xiangrui Meng, Fotios Koskeridis, Andrea Georgiou, Lili Yu, Harry Campbell, Evropi Theodoratou, Xue Li
Summary: Phenome-wide association study (PheWAS) has been increasingly used to identify novel genetic associations across a wide spectrum of phenotypes. This systematic review provides a comprehensive overview of PheWAS methodology, discussing its advantages and challenges, and offering potential implications for future studies. The majority of PheWAS studies included over 10,000 participants, defined phenotypes based on electronic medical records data, used genetic variants as predictors, and conducted replication analysis to validate findings.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Psychiatry
Sandra Sanchez-Roige, Mariela Jennings, Hayley H. A. Thorpe, Jazlene Mallari, Lieke C. van der Werf, Sevim B. Bianchi, Yuye Huang, Calvin Lee, Travis T. Mallard, Samuel A. Barnes, Jin Yi Wu, Amanda M. Barkley-Levenson, Ely C. Boussaty, Cedric E. Snethlage, Danielle Schafer, Zeljana Babic, Boyer D. Winters, Katherine E. Watters, Thomas Biederer, Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Daniella Coker, Gabriel Cuellar Partida, Devika Dhamija, Sayantan Das, Teresa Filshtein, Kipper Fletez-Brant, Will Freyman, Karl Heilbron, Pooja M. Gandhi, Karl Heilbron, Barry Hicks, David A. Hinds, Ethan M. Jewett, Yunxuan Jiang, Katelyn Kukar, Keng-Han Lin, Maya Lowe, Jey C. McCreight, Matthew H. McIntyre, Steven J. Micheletti, Meghan E. Moreno, Joanna L. Mountain, Priyanka Nandakumar, Elizabeth S. Noblin, Jared O'Connell, Aaron A. Petrakovitz, G. David Poznik, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Alejandro Hernandez, Corinna Wong, Christophe Toukam Tchakoute, James Mackillop, David N. Stephens, Sarah L. Elson, Pierre Fontanillas, Jibran Y. Khokhar, Jared W. Young, Abraham A. Palmer
Summary: Impulsivity is a heritable trait associated with various forms of psychopathology, and the gene CADM2 is found to be implicated in it. Genome-wide association studies and mouse experiments have confirmed this finding. This study further explores the role of CADM2 in impulsivity and its link with other psychiatric and somatic traits.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Shun Li, C. M. Schooling
Summary: In addition to their well-known cardiovascular disease prevention benefits, statins have sex-specific pleiotropic effects. Genetically mimicking statins was found to have inverse associations with lipid traits, especially in women, and was also related to platelet attributes, serum calcium, and sex hormone-binding globulin.
Article
Cardiac & Cardiovascular Systems
Seyedeh Maryam Zekavat, Vineet K. Raghu, Mark Trinder, Yixuan Ye, Satoshi Koyama, Michael C. Honigberg, Zhi Yu, Akhil Pampana, Sarah Urbut, Sara Haidermota, Declan P. O'Regan, Hongyu Zhao, Patrick T. Ellinor, Ayellet V. Segre, Tobias Elze, Janey L. Wiggs, James Martone, Ron A. Adelman, Nazlee Zebardast, Lucian Del Priore, Jay C. Wang, Pradeep Natarajan
Summary: Using machine learning to assess retinal vasculature, this study found that low retinal vascular density and fractal dimension were associated with increased risk for various diseases, and identified novel genes linked to angiogenesis and inflammation.
Article
Computer Science, Hardware & Architecture
Xiaojie Zhu, Erman Ayday, Roman Vitenberg
Summary: Due to the privacy concerns of genomic and phenotype data, data owners often outsource their data to cloud service providers (CSPs) for storage and analysis. In this work, we propose a solution that enables privacy-preserving search and analysis over encrypted genomic and phenotype data owned by multiple hospitals. We introduce encryption mechanisms for phenotype data and multi-key fully homomorphic encryption for genomic data, allowing efficient identification of case/control groups and computation of GWAS statistics without privacy violations.
IEEE TRANSACTIONS ON DEPENDABLE AND SECURE COMPUTING
(2023)
Review
Biochemistry & Molecular Biology
Frederick J. Boehm, Xiang Zhou
Summary: Genome-wide association studies have provided numerous associations for common diseases and complex traits. Mendelian randomization methods, utilizing SNP associations, help uncover causal relationships between complex traits. The availability of GWAS summary statistics has motivated the development of new Mendelian randomization methods with relaxed causality assumptions, offering opportunities for robust biological discoveries.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Clinical Neurology
Shogo Dofuku, Kyuto Sonehara, Satoru Miyawaki, Saori Sakaue, Hideaki Imai, Masahiro Shimizu, Hiroki Hongo, Yuki Shinya, Kenta Ohara, Yu Teranishi, Atsushi Okano, Hideaki Ono, Hirofumi Nakatomi, Akira Teraoka, Kenichi Yamamoto, Yuichi Maeda, Takuro Nii, Toshihiro Kishikawa, Ken Suzuki, Jun Hirata, Meiko Takahashi, Koichi Matsuda, Atsushi Kumanogoh, Fumihiko Matsuda, Yukinori Okada, Nobuhito Saito
Summary: This study conducted the first genome-wide association study (GWAS) of intracranial artery stenosis (ICAS) in a Japanese population. They identified a functional variant of RNF2J3, rs112735431, that was significantly associated with ICAS. Furthermore, they found that this variant was also associated with high blood pressure and angina.
TRANSLATIONAL STROKE RESEARCH
(2023)
Review
Engineering, Multidisciplinary
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
Summary: Glycosylation plays a crucial role in the properties and functions of proteins, and alterations in protein glycosylation are implicated in human diseases. However, the regulatory mechanisms of glycosylation in humans are still poorly understood, limiting the clinical applications of human glycobiology. Human genetics and genomics provide important tools for studying human in vivo glycobiology. This review summarizes the current state of human populational glycogenomics.
