Article
Clinical Neurology
Manuela M. X. Tan, Michael A. Lawton, Edwin Jabbari, Regina H. Reynolds, Hirotaka Iwaki, Cornelis Blauwendraat, Sofia Kanavou, Miriam Pollard, Leon Hubbard, Naveed Malek, Katherine A. Grosset, Sarah L. Marrinan, Nin Bajaj, Roger A. Barker, David J. Burn, Catherine Bresner, Thomas Foltynie, Nicholas W. Wood, Caroline H. Williams-Gray, John Hardy, Michael A. Nalls, Andrew B. Singleton, Nigel M. Williams, Yoav Ben-Shlomo, Michele T. M. Hu, Donald G. Grosset, Maryam Shoai, Huw R. Morris
Summary: The study found that genetic variants associated with Parkinson's disease risk are not linked to disease progression. The APOE epsilon 4 tagging variant was significantly associated with cognitive progression, while ATP8B2 gene showed a nominal association with motor progression. The new method shows promise in improving the measurement of symptom progression in PD.
MOVEMENT DISORDERS
(2021)
Review
Cell Biology
Ruben Fernandez-Santiago, Manu Sharma
Summary: After fifteen years of GWAS in Parkinson's disease, progress has been made towards understanding disease mechanisms and improving clinical applicability. Future strategies should focus on underrepresented populations and enhancing disease prediction. Advanced GWAS designs can define genetic risk profiles and facilitate neuroprotective clinical trials.
AGEING RESEARCH REVIEWS
(2022)
Review
Cell Biology
Carina Mauersberger, Heribert Schunkert, Hendrik B. Sager
Summary: While the importance of inflammation in atherosclerosis is recognized, the exact molecular processes remain unclear. Modern genetics, specifically genome-wide association studies, have revealed many loci related to inflammatory processes in coronary artery disease, but translating these findings into specific molecular mechanisms is still challenging.
Review
Physiology
Roddy Walsh, Sean J. Jurgens, Jeanette Erdmann, Connie R. Bezzina
Summary: Genome-wide association studies (GWAS) have identified common genetic variants associated with traits and diseases, providing insights into genetic architecture, correlations across traits and diseases, and potential clinical applications. The utilization of GWAS in cardiovascular diseases and associated phenotypic traits has been facilitated by multicenter registry studies and large biobank data sets. However, challenges still exist in this field and need to be addressed.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Gastroenterology & Hepatology
Connor A. Emdin, Mary Haas, Veeral Ajmera, Tracey G. Simon, Julian Homburger, Cynthia Neben, Lan Jiang, Wei-Qi Wei, Qiping Feng, Alicia Zhou, Joshua Denny, Kathleen Corey, Rohit Loomba, Sekar Kathiresan, Amit Khera
Summary: This study identified 12 independent genetic variants, including 7 newly identified ones, that confer risk for cirrhosis. A polygenic score based on these variants can identify a subset of the population at substantially increased risk, particularly those susceptible to the hepatotoxic effects of excess alcohol consumption or obesity.
Article
Biochemical Research Methods
Kleanthi Lakiotaki, Zaharias Papadovasilakis, Vincenzo Lagani, Stefanos Fafalios, Paulos Charonyktakis, Michail Tsagris, Ioannis Tsamardinos
Summary: This article introduces an automated machine learning approach customized for genomic data, which can provide reliable predictive and diagnostic models and discover genetic variants with higher predictive performance. The approach can also compute individual risk prediction scores, generalize to new, unseen data, and better differentiate causal variants from other highly correlated variants.
Article
Multidisciplinary Sciences
Abbas Saad Alatrany, Wasiq Khan, Abir Hussain, Dhiya Al-Jumeily
Summary: The increasing incidence of Alzheimer's disease (AD) poses socioeconomic challenges. In this study, a hybrid feature selection approach and neural network models are used to predict AD. The approach outperformed existing methods with 99% accuracy and f1-score, providing impactful outcomes for other chronic diseases.
Review
Cardiac & Cardiovascular Systems
Tejas P. Singh, Matt A. Field, Matthew J. Bown, Gregory T. Jones, Jonathan Golledge
Summary: This study systematically reviewed previous AAA GWAS and identified 33 SNPs associated with AAA diagnosis at genome-wide significance. However, the association between SNPs and AAA growth was not adequately examined. Previous GWAS have various design limitations, such as inconsistent case and control ascertainment and limited phenotyping of the AAAs.
Review
Immunology
Rochi Saurabh, Cesaire J. K. Fouodo, Inke R. R. Konig, Hauke Busch, Inken Wohlers
Summary: This paper reviews current publicly available GWAS and PGS data on autoimmune diseases, summarizes the diseases investigated and the respective studies conducted, and provides an overview of the genetic data and autoimmune disease patients in the UK Biobank. The study finds that only the more prevalent autoimmune diseases are covered by both GWAS and PGS catalogs in the UK Biobank.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Paola Leon-Mimila, Hugo Villamil-Ramirez, Luis R. Macias-Kauffer, Leonor Jacobo-Albavera, Blanca E. Lopez-Contreras, Rosalinda Posadas-Sanchez, Carlos Posadas-Romero, Sandra Romero-Hidalgo, Sofia Moran-Ramos, Mayra Dominguez-Perez, Marisol Olivares-Arevalo, Priscilla Lopez-Montoya, Roberto Nieto-Guerra, Victor Acuna-Alonzo, Gaston Macin-Perez, Rodrigo Barquera-Lozano, Blanca E. Del-Rio-Navarro, Israel Gonzalez-Gonzalez, Francisco Campos-Perez, Francisco Gomez-Perez, Victor J. Valdes, Alicia Sampieri, Juan G. Reyes-Garcia, Miriam Del C. Carrasco-Portugal, Francisco J. Flores-Murrieta, Carlos A. Aguilar-Salinas, Gilberto Vargas-Alarcon, Diana Shih, Peter J. Meikle, Anna C. Calkin, Brian G. Drew, Luis Vaca, Aldons J. Lusis, Adriana Huertas-Vazquez, Teresa Villarreal-Molina, Samuel Canizales-Quinteros
Summary: The study identified a genetic variant in the SIDT2 gene associated with HDL-C levels and cardiovascular risk in Mexicans, with implications for cholesterol and lipoprotein metabolism. The SIDT2/Val636Ile variant was more common in Native American populations and linked to lower LDL-C and ApoB levels. Further investigation showed that the variant affects cholesterol transport function, highlighting SIDT2 as a new player in human lipid metabolism.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jonathan P. Allen, Evan Snitkin, Nathan B. Pincus, Alan R. Hauser
Summary: The advent of inexpensive and rapid sequencing technologies has allowed for unprecedented generation of bacterial whole-genome sequences. This has led to a greater understanding of genetic diversity within bacterial species and its implications for virulence. Comparative genomic approaches, such as genome-wide association studies and machine learning, are being used to identify novel virulence factors.
TRENDS IN MICROBIOLOGY
(2021)
Article
Clinical Neurology
Ryoichi Nakamura, Genki Tohnai, Masahiro Nakatochi, Naoki Atsuta, Hirohisa Watanabe, Daisuke Ito, Masahisa Katsuno, Akihiro Hirakawa, Yuishin Izumi, Mitsuya Morita, Takehisa Hirayama, Osamu Kano, Kazuaki Kanai, Nobutaka Hattori, Akira Taniguchi, Naoki Suzuki, Masashi Aoki, Ikuko Iwata, Ichiro Yabe, Kazumoto Shibuya, Satoshi Kuwabara, Masaya Oda, Rina Hashimoto, Ikuko Aiba, Tomohiko Ishihara, Osamu Onodera, Toru Yamashita, Koji Abe, Kouichi Mizoguchi, Toshio Shimizu, Yoshio Ikeda, Takanori Yokota, Kazuko Hasegawa, Fumiaki Tanaka, Kenji Nakashima, Ryuji Kaji, Jun-ichi Niwa, Manabu Doyu, Chikashi Terao, Shiro Ikegawa, Koki Fujimori, Shiho Nakamura, Fumiko Ozawa, Satoru Morimoto, Kazunari Onodera, Takuji Ito, Yohei Okada, Hideyuki Okano, Gen Sobue
Summary: In this study, three novel loci (FGF1, THSD7A, and LRP1) were identified to be associated with the survival of sporadic ALS patients. Decreased mRNA expression of FGF1 and THSD7A were also observed, which correlated with reduced viability of induced pluripotent stem cell-derived motor neurons from ALS patients.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Physiology
Travis T. Mallard, Andrew D. Grotzinger, Jordan W. Smoller
Summary: Genome-wide association studies have led to reproducible discoveries in psychiatric genetics, identifying hundreds of common genetic variants associated with mental disorders. These findings have the potential to inform the development of new therapeutics, stratify at-risk patients, and possibly revise classification systems in psychiatry. The review summarizes GWAS findings at three levels of analysis: genome-wide architecture, networks and pathways, and individual variants/genes. Three themes emerge: heritability and polygenic nature of psychiatric phenotypes, the importance of neuronal biology and early neurodevelopment, and the involvement of synaptic structure and function in psychopathology. The implications of GWAS results for psychiatry and future directions are also discussed.
PHYSIOLOGICAL REVIEWS
(2023)
Review
Pathology
Xu Cheng, Jiayu Shi, Zhonglin Jia, Pin Ha, Chia Soo, Kang Ting, Aaron W. James, Bing Shi, Xinli Zhang
Summary: This review summarizes the findings from GWASs on the specific NELL1 single-nucleotide polymorphisms in various disorders in humans, illustrating the wide range of potential effects of a single gene on the pathogenesis of multiple disorders.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Gabriela Franca Oliveira, Ana Carolina Campana Nascimento, Camila Ferreira Azevedo, Mauricio de Oliveira Celeri, Lais Mayara Azevedo Barroso, Isabela de Castro Sant'Anna, Jose Marcelo Soriano Viana, Marcos Deon Vilela de Resende, Moyses Nascimento
Summary: The study aimed to evaluate the performance of Quantile Regression (QR) in Genome-Wide Association Studies (GWAS) for detecting QTLs associated with phenotypic traits. Simulated data was used with traits of different heritability levels and controlled by different numbers of QTLs. QR models showed higher detection power and lower false positive rate compared to the General Linear Model (GLM). QR had a high detection power in scenarios with low heritability and can effectively detect QTLs even with a small number of individuals.
SCIENTIFIC REPORTS
(2023)
Article
Geriatrics & Gerontology
Celia Kun-Rodrigues, Tatiana Orme, Susana Carmona, Dena G. Hernandez, Owen A. Ross, John D. Eicher, Claire Shepherd, Laura Parkkinen, Lee Darwent, Michael G. Heckman, Sonja W. Scholz, Juan C. Troncoso, Olga Pletnikova, Ted Dawson, Liana Rosenthal, Olaf Ansorge, Jordi Clarimonm, Alberto Lleo, Estrella Morenas-Rodriguez, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Ekaterina Rogaeva, Peter St George-Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, Geidy E. Serrano, Thomas G. Beach, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J. Cairns, John C. Morris, Stuart Pickering-Brown, David Mann, Glenda M. Halliday, John Hardy, John Q. Trojanowski, Dennis W. Dickson, Andrew Singleton, David J. Stone, Rita Guerreiro, Jose Bras
NEUROBIOLOGY OF AGING
(2019)
Review
Clinical Neurology
Oluwafemi G. Oluwole, Helena Kuivaniemi, Jonathan A. Carr, Owen A. Ross, Matthew O. B. Olaogun, Soraya Bardien, Morenikeji A. Komolafe
PARKINSONISM & RELATED DISORDERS
(2019)
Article
Clinical Neurology
Octavio A. Santos, Otto Pedraza, John A. Lucas, Ranjan Duara, Maria T. Greig-Custo, Fadi S. Hanna Al-Shaikh, Amanda M. Liesinger, Kevin F. Bieniek, Kelly M. Hinkle, Elizabeth R. Lesser, Julia E. Crook, Minerva M. Carrasquillo, Owen A. Ross, Nilufer Ertekin-Taner, Neill R. Graff-Radford, Dennis W. Dickson, Melissa E. Murray
ALZHEIMERS & DEMENTIA
(2019)
Article
Clinical Neurology
Patrick R. Blackburn, Wen-Lang Lin, David A. Miller, Oswaldo Lorenzo-Betancor, Emily S. Edwards, Michael T. Zimmermann, Luca P. Farrugia, William D. Freeman, Alexandra I. Soto, Ronald L. Walton, Eric W. Klee, Paldeep S. Atwal, Roshini S. Abraham, Daniel D. Billadeau, Owen A. Ross, Dennis W. Dickson, James F. Meschia
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2019)
Editorial Material
Clinical Neurology
Eva-Juliane Vollstedt, Meike Kasten, Christine Klein
ANNALS OF NEUROLOGY
(2019)
Article
Clinical Neurology
Rebecca R. Valentino, Shunsuke Koga, Michael G. Heckman, Danielle E. C. Brushaber, Nancy N. Diehl, Ronald L. Walton, Dennis W. Dickson, Owen A. Ross
MOVEMENT DISORDERS
(2020)
Article
Clinical Neurology
Angela B. Deutschlander, Takuya Konno, Alexandra Soto-Beasley, Ronald L. Walton, Jay A. van Gerpen, Ryan J. Uitti, Michael G. Heckman, Zbigniew K. Wszolek, Owen A. Ross
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)
Letter
Clinical Neurology
Amica C. Mueller-Nedebock, Morenikeji A. Komolafe, Michael B. Fawale, Jonathan A. Carr, Francois H. van Der Westhuizen, Owen A. Ross, Soraya Bardien
MOVEMENT DISORDERS
(2021)
Review
Clinical Neurology
Etienne Leveille, Owen A. Ross, Ziv Gan-Or
Summary: The MAPT gene encodes the tau protein, which is associated with neurofibrillary tangles and various tauopathies and synucleinopathies. Understanding the role of MAPT variations in these disorders is crucial for elucidating the pathogenesis and phenotype of tau-related diseases and developing targeted therapies. Furthermore, evidence suggests interactions between tau and alphasynuclein at a molecular level, potentially impacting the neurodegenerative process.
PARKINSONISM & RELATED DISORDERS
(2021)
Letter
Clinical Neurology
Lukasz M. Milanowski, Olajumoke Oshinaike, Ronald L. Walton, Alexandra I. Soto-Beasley, Rana Hanna Al-Shaikh, Audrey J. Strongosky, Owen A. Ross, Zbigniew K. Wszolek, Shamsideen Abayomi Ogun
MOVEMENT DISORDERS
(2021)
Letter
Clinical Neurology
Diana A. Olszewska, Allan McCarthy, Alexandra I. Soto-Beasley, Ronald L. Walton, Owen A. Ross, Tim Lynch
JOURNAL OF MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Paolo Reho, Shunsuke Koga, Zalak Shah, Ruth Chia, Rosa Rademakers, Clifton L. Dalgard, Bradley F. Boeve, Thomas G. Beach, Dennis W. Dickson, Owen A. Ross, Sonja W. Scholz
Summary: This study aimed to evaluate pathogenic variants in GRN among Lewy body dementia (LBD) patients and found an enrichment of GRN loss-of-function mutations in the cases.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Franziska Hopfner, Anja K. Tietz, Viktoria C. Ruf, Owen A. Ross, Shunsuke Koga, Dennis Dickson, Adriano Aguzzi, Johannes Attems, Thomas Beach, Allison Beller, William P. Cheshire, Vivianna van Deerlin, Paula Desplats, Guenther Deuschl, Charles Duyckaerts, David Ellinghaus, Valentin Evsyukov, Margaret Ellen Flanagan, Andre Franke, Matthew P. Frosch, Marla Gearing, Ellen Gelpi, Jay A. van Gerpen, Bernardino Ghetti, Jonathan D. Glass, Lea T. Grinberg, Glenda Halliday, Ingo Helbig, Matthias Hollerhage, Inge Huitinga, David John Irwin, Dirk C. Keene, Gabor G. Kovacs, Edward B. Lee, Johannes Levin, Maria J. Marti, Ian Mackenzie, Ian McKeith, Catriona Mclean, Brit Mollenhauer, Manuela Neumann, Kathy L. Newell, Alex Pantelyat, Manuela Pendziwiat, Annette Peters, Laura Molina Porcel, Alberto Rabano, Radoslav Matej, Alex Rajput, Ali Rajput, Regina Reimann, William K. Scott, William Seeley, Sashika Selvackadunco, Tanya Simuni, Christine Stadelmann, Per Svenningsson, Alan Thomas, Claudia Trenkwalder, Claire Troakes, John Q. Trojanowski, Ryan J. Uitti, Charles L. White, Zbigniew K. Wszolek, Tao Xie, Teresa Ximelis, Justo Yebenes, Ulrich Mueller, Gerard D. Schellenberg, Jochen Herms, Gregor Kuhlenbaumer, Gunter Hoeglinger
Summary: Multiple System Atrophy is a rare neurodegenerative disease characterized by alpha-synuclein aggregation in glial cytoplasmic inclusions. By studying autopsy-confirmed cases, it was found that rs16859966 on chromosome 3, rs7013955 on chromosome 8, and rs116607983 on chromosome 4 are the most strongly disease-associated markers.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Hiroaki Sekiya, Shunsuke Koga, Aya Murakami, Michael Deture, Owen A. Ross, Ryan J. Uitti, William P. Cheshire, Zbigniew K. Wszolek, Dennis W. Dickson
Summary: Comorbid pathologies are uncommon in multiple system atrophy (MSA), even in advanced age, indicating its uniqueness among neurodegenerative disorders. These comorbid pathologies have minimal clinical impact on MSA.
MOVEMENT DISORDERS
(2023)
Article
Cell Biology
Tania F. Gendron, Mohammed K. Badi, Michael G. Heckman, Karen R. Jansen-West, George K. Vilanilam, Patrick W. Johnson, Alexander R. Burch, Ronald L. Walton, Owen A. Ross, Thomas G. Brott, Timothy M. Miller, James D. Berry, Katharine A. Nicholson, Zbigniew K. Wszolek, Bjorn E. Oskarsson, Kevin N. Sheth, Lauren H. Sansing, Guido J. Falcone, Brett L. Cucchiara, James F. Meschia, Leonard Petrucelli
SCIENCE TRANSLATIONAL MEDICINE
(2020)