Article
Hematology
Marisol Herrera-Rivero, Monika Stoll, Jana-Charlotte Hegenbarth, Frank Ruehle, Verena Limperger, Ralf Junker, Andre Franke, Per Hoffmann, Maria Shneyder, Michael Stach, Ulrike Nowak-Goettl
Summary: This study identified 20 new susceptibility genes for VTE, which may impact the production and prothrombotic functions of platelets, endothelial cells, white blood cells, and red blood cells. Most of these genes have been previously associated with cardiovascular diseases and/or risk factors for VTE.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Genetics & Heredity
Hossam Hodeib, Amira Youssef, Alzahraa A. Allam, Amal Selim, Mohamed A. Tawfik, Mohammed F. Abosamak, Ahmed Esam, Mohamed S. Abd Elghafar, Sameh Samir, Ola A. ELshora
Summary: The study found that patients with >= 3 risk alleles were associated with a higher risk of VTE recurrence compared to those with <= 2 risk alleles (the reference group) (HR 2.5, 95% CI 1.48-4.21) (p = 0.001). Patients with GRS >= 3 had a significantly shorter time recurrence free survival (43.07 months) compared to the low risk group of patients with GRS (0-2) (p < 0.001). The GRS model could be effective in risk stratification of VTE patients and genetic risk profiling could be used for predicting VTE recurrence.
Article
Clinical Neurology
Farid Rajabli, Giuseppe Tosto, Kara L. Hamilton-Nelson, Brian W. Kunkle, Badri N. Vardarajan, Adam Naj, Patrice G. Whitehead, Olivia K. Gardner, William S. Bush, Sanjeev Sariya, Richard P. Mayeux, Lindsay A. Farrer, Michael L. Cuccaro, Jeffrey M. Vance, Anthony J. Griswold, Gerard D. Schellenberg, Jonathan L. Haines, Goldie S. Byrd, Christiane Reitz, Gary W. Beecham, Margaret A. Pericak-Vance, Eden R. Martin
Summary: This study used admixture mapping and ancestry-aware regression analysis to study Alzheimer's disease in African American individuals. The study identified genetic regions associated with Alzheimer's disease and discovered interesting genes.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Klodian Dhana, Lisa L. Barnes, Xiaoran Liu, Puja Agarwal, Pankaja Desai, Kristin R. Krueger, Thomas M. Holland, Shannon Halloway, Neelum T. Aggarwal, Denis A. Evans, Kumar B. Rajan
Summary: The study found that the APOE ε 4 allele is associated with cognitive decline, but adherence to a healthy lifestyle can slow down this decline in individuals carrying this gene. Both African Americans and European Americans showed a trend of slower cognitive decline when following a healthy lifestyle.
ALZHEIMERS & DEMENTIA
(2022)
Article
Cardiac & Cardiovascular Systems
Florian Thibord, Derek Klarin, Jennifer A. Brody, Ming-Huei Chen, Michael G. Levin, Daniel Chasman, Ellen L. Goode, Kristian Hveem, Maris Teder-Laving, Angel Martinez-Perez, Dylan Aissi, Delphine Daian-Bacq, Kaoru Ito, Pradeep Natarajan, Pamela L. Lutsey, Girish N. Nadkarni, Paul S. de Vries, Gabriel Cuellar-Partida, Brooke N. Wolford, Jack W. Pattee, Charles Kooperberg, Sigrid K. Braekkan, Ruifang Li-Gao, Noemie Saut, Corriene Sept, Marine Germain, Renae L. Judy, Kerri L. Wiggins, Darae Ko, Christopher J. O'Donnell, Kent D. Taylor, Franco Giulianini, Mariza De Andrade, Therese H. Nost, Anne Boland, Jean-Philippe Empana, Satoshi Koyama, Thomas Gilliland, Ron Do, Jennifer E. Huffman, Xin Wang, Wei Zhou, Jose Manuel Soria, Juan Carlos Souto, Nathan Pankratz, Jeffery Haessler, Kristian Hindberg, Frits R. Rosendaal, Constance Turman, Robert Olaso, Rachel L. Kember, Traci M. Bartz, Julie A. Lynch, Susan R. Heckbert, Sebastian M. Armasu, Ben Brumpton, David M. Smadja, Xavier Jouven, Issei Komuro, Katharine R. Clapham, Ruth J. F. Loos, Cristen J. Willer, Maria Sabater-Lleal, James S. Pankow, Alexander P. Reiner, Vania M. Morelli, Paul M. Ridker, Astrid van Hylckama Vlieg, Jean-Francois Deleuze, Peter Kraft, Daniel J. Rader, Kyung Min Lee, Bruce M. Psaty, Anne Heidi Skogholt, Joseph Emmerich, Pierre Suchon, Stephen S. Rich, Ha My T. Vy, Weihong Tang, Rebecca D. Jackson, John-Bjarne Hansen, Pierre-Emmanuel Morange, Christopher Kabrhel, David-Alexandre Tregouet, Scott M. Damrauer, Andrew D. Johnson, Nicholas L. Smith
Summary: This study identified new genetic loci associated with VTE by using cross-ancestry genomic resources. The findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.
Review
Hematology
Birgitte G. Tondel, Vania M. Morelli, John-Bjarne Hansen, Sigrid K. Braekkan
Summary: This systematic review identifies several potential risk factors and predictors for VTE in individuals with ischemic stroke. However, further confirmation is needed as there were few high-quality studies on each factor.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Ophthalmology
Brian S. Cole, Harini V. Gudiseva, Maxwell Pistilli, Rebecca Salowe, Caitlin P. McHugh, Michael C. Zody, Venkata R. M. Chavali, Gui Shuang Ying, Jason H. Moore, Joan M. O'Brien
Summary: This study examines the association of autosomal ancestry with POAG risk in a large cohort of self-identified African Americans. The results show that a higher degree of African ancestry is associated with an increased risk of POAG. Additionally, it is found that both known POAG single nucleotide polymorphisms and an omnigenic ancestry effect influence POAG risk.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Medicine, General & Internal
Huijie Wang, Mary Cushman, Frits R. Rosendaal, Astrid van Hylckama Vlieg
Summary: This study found that a remote history of venous thrombosis (VT) is associated with an increased risk of VT in older individuals, providing valuable information for clinicians to advise patients on VT prevention.
Article
Hematology
Jiayu Wang, Jiangshan Tan, Lu Hua, Qiping Sheng, Xianwei Huang, Ping Liu
Summary: Obesity, especially abdominal obesity, is associated with an increased risk of venous thromboembolism and pulmonary embolism. This study used genetic data and summary-level epidemiological data to demonstrate a causal relationship between waist circumference/hip circumference and the risk of VTE and PE. Measures to reduce obesity may help decrease the incidence of VTE and PE.
THROMBOSIS AND HAEMOSTASIS
(2023)
Review
Cell Biology
Viktoria Muster, Thomas Gary
Summary: Glioblastoma patients have a high risk of developing venous thromboembolism, making therapeutic anticoagulation challenging with limited data available for this vulnerable patient group.
Article
Clinical Neurology
Liqi Shu, Ekaterina Bakradze, Setareh Salehi Omran, James Giles, Jordan Amar, Nils Henninger, Marwa Elnazeir, Ava Liberman, Khadean Moncrieffe, Jenny Rotblat, Richa Sharma, Yee Cheng, Adeel S. Zubair, Alexis Simpkins, Grace Li, Justin Kung, Dezaray Perez, Mirjam R. Heldner, Adrian Scutelnic, Rascha Von Martial, Bernhard Siepen, Aaron Rothstein, Ossama Khazaal, David Do, Sami Al Kasab, Line Abdul Rahman, Eva A. Mistry, Deborah Kerrigan, Hayden Lafever, Thanh N. Nguyen, Piers Klein, Hugo J. Aparicio, Jennifer A. Frontera, Lindsey Kuohn, Shashank Agarwal, Christoph Stretz, Narendra Kala, Sleiman ElJamal, Allison Chang, Shawna Cutting, Fransisca Indraswari, Adam de Havenon, Varsha Muddasani, Teddy Wu, Duncan Wilson, Amre Nouh, Daniyal Asad, Abid Qureshi, Justin Moore, Pooja Khatri, Yasmin Aziz, Bryce Casteigne, Muhib Khan, Yao Cheng, Brian MacGrory, Martin Weiss, Dylan Ryan, Maria Cristina Vedovati, Maurizio Paciaroni, James Siegler, Scott Kamen, Siyuan Yu, Christopher Leon Guerrero, Eugenie Atallah, Gian Marco De Marchis, Alex Brehm, Tolga Dittrich, Marios Psychogios, Ronald Alvarado-Dyer, Tareq Kass-Hout, Shyam Prabhakaran, Tristan Honda, David Liebeskind, Karen Furie, Shadi Yaghi
Summary: This study aimed to identify predictors of recurrent venous thrombosis in patients with CVT. The study found that Black race, history of VTE, and the presence of one or more positive antiphospholipid antibodies were associated with recurrent venous thrombosis among patients with CVT.
Article
Hematology
Max D. Hazeltine, Robert D. Guber, Hannah Buettner, Jon D. Dorfman
Summary: Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. The study supports the use of the Caprini risk assessment model in the trauma population for effective risk stratification.
THROMBOSIS RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Nicholas A. Marston, Giorgio E. M. Melloni, Yared Gurmu, Marc P. Bonaca, Frederick K. Kamanu, Carolina Roselli, Christina Lee, Ilaria Cavallari, Robert P. Giugliano, Benjamin M. Scirica, Deepak L. Bhatt, Philippe Gabriel Steg, Marc Cohen, Robert F. Storey, Anthony C. Keech, Itamar Raz, Ofri Mosenzon, Eugene Braunwald, Steven A. Lubitz, Patrick T. Ellinor, Marc S. Sabatine, Christian T. Ruff
Summary: The study tested a genetic risk score for predicting venous thromboembolism in patients with cardiometabolic disease. Results showed that the genetic risk score was significantly associated with VTE risk, and could independently predict the occurrence of VTE in this patient population.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2021)
Review
Virology
Quan Zhang, Fei Peng, Meizhi Li, Qiong Yi, Wei Tang, Shangjie Wu
Summary: HIV patients have a higher risk of developing venous thromboembolism (VTE), which is the third most common cardiovascular condition in this population. Understanding the epidemiology, pathophysiology, molecular mechanisms, and therapeutic interventions of VTE in HIV is crucial for optimizing treatment outcomes and balancing risks and benefits.
Article
Medicine, General & Internal
JunQing Xie, Albert Prats-Uribe, Qi Feng, YunHe Wang, Dipender Gill, Roger Paredes, Dani Prieto-Alhambra
Summary: This population-based cohort study found that ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE, and factor V Leiden thrombophilia was additionally associated with double the risk. These findings are important for emphasizing the need for vaccination, informing VTE risk stratification, and calling for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.
JAMA INTERNAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Zachary F. Gerring, Jackson G. Thorp, Eric R. Gamazon, Eske M. Derks
Summary: Transcriptome-wide association study revealed the functional gene mechanisms underlying psychiatric disorders and substance use phenotypes using gene expression data.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
Vasiliki Thomeas-McEwing, Mitchell A. Psotka, Eric R. Gamazon, Paula Friedman, Anuar Konkashbaev, Michiaki Kubo, Yusuke Nakamura, Mark J. Ratain, Raymond L. Benza, Nancy J. Cox, Mardi Gomberg-Maitland, Michael L. Maitland
Summary: The study aimed to identify new biologically-based predictors of prostacyclin treatment response heterogeneity for patients with pulmonary arterial hypertension. Genome-wide association study and in vitro assays were conducted to identify candidate genes and their effects on prostacyclin-induced vasodilation. The findings suggest that specific genetic variants may affect treatment response and right ventricular function in patients with pulmonary arterial hypertension.
PHARMACOGENETICS AND GENOMICS
(2022)
Article
Pharmacology & Pharmacy
Heidi E. Steiner, Kelvin Carrasquillo Carrion, Jason B. Giles, Abiel Roche Lima, Kevin Yee, Xiaoxiao Sun, Larisa H. Cavallari, Minoli A. Perera, Jorge Duconge, Jason H. Karnes
Summary: The accuracy of warfarin dose prediction algorithms can be improved by including data from diverse populations in genetic studies, as demonstrated by this study. It also highlights the technical challenges of including diverse, especially admixed populations in pharmacogenomic research.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Pharmacology & Pharmacy
Guang Yang, Mrinal Mishra, Minoli A. Perera
Summary: Given the limitations of GWASs, including the majority of significant associations found in the non-coding region of the genome and a lack of diversity in studies, we need to utilize multi-omics approaches to gain a deeper understanding of the biological mechanisms underlying diseases and drug responses, and how to include diverse populations.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Honghong Zhang, Cristina Alarcon, Larisa H. H. Cavallari, Edith Nutescu, Gemma L. L. Carvill, Minoli A. A. Perera, Wenndy Hernandez
Summary: This study conducted the first genome-wide analysis of copy number variants (CNVs) in African Americans, revealing CNVRs associated with warfarin dose requirement and VTE risk.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Medicine, General & Internal
Kierstin Kennedy, Heather Briggs, Matthew Tuck
JOURNAL OF HOSPITAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Jibril B. Hirbo, Francesca Pasutto, Eric R. Gamazon, Patrick Evans, Priyanka Pawar, Daniel Berner, Julia Sealock, Ran Tao, Peter S. Straub, Anuar I. Konkashbaev, Max A. Breyer, Ursula Schloetzer-Schrehardt, Andre Reis, Milam A. Brantley Jr, Chiea C. Khor, Karen M. Joos, Nancy J. Cox
Summary: Exfoliation syndrome (XFS) is an age-related disorder that causes the accumulation of abnormal extracellular material in the body, leading to ocular manifestations and secondary glaucoma. A global meta-analysis identified seven loci near LOXL1 that are strongly associated with XFS. The study conducted transcriptomic wide association studies and experimental analysis to reveal the role of connective tissues and inflammation pathways in the development of XFS.
Article
Cell Biology
Timothy C. Kenny, Artem Khan, Yeeun Son, Lishu Yue, Soren Heissel, Anurag Sharma, H. Amalia Pasolli, Yuyang Liu, Eric R. Gamazon, Hanan Alwaseem, Richard K. Hite, Kivanc Birsoy
Summary: A genetic analysis linking serum metabolites to membrane transporters revealed a connection between FLVCR1 and phosphocholine. FLVCR1 loss impairs choline metabolism and leads to mitochondrial defects and upregulation of the integrated stress response. The findings suggest FLVCR1 as a major choline transporter in mammals and provide a platform to discover substrates for unknown metabolite transporters.
Article
Psychiatry
Damian J. Woodward, Jackson G. Thorp, Wole Akosile, Jue-Sheng Ong, Eric R. Gamazon, Eske M. Derks, Zachary F. Gerring
Summary: Anxiety disorders are prevalent and heritable neuropsychiatric diseases. By integrating genome-wide association study (GWAS) and functional genomic data, researchers identified genes associated with anxiety and discovered potential drug targets for anxiety treatment through drug repurposing.
PSYCHIATRY RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sylvia Hartmann, Summaira Yasmeen, Benjamin M. Jacobs, Spiros Denaxas, Munir Pirmohamed, Eric R. Gamazon, Mark J. Caulfield, Harry Hemingway, Maik Pietzner, Claudia Langenberg
Summary: The study identified three novel genomic regions related to Raynaud's phenomenon risk, prioritized candidate causal genes, and revealed a likely detrimental effect of low fasting glucose levels on RP risk. The research also highlighted opportunities for drug repurposing and provided robust evidence for a strong genetic contribution to RP.
NATURE COMMUNICATIONS
(2023)
Article
Computer Science, Artificial Intelligence
Ramon Vinas, Chaitanya K. Joshi, Dobrik Georgiev, Phillip Lin, Bianca Dumitrascu, Eric R. Gamazon, Pietro Lio
Summary: Vinas et al. propose a neural network for multi-tissue imputation of gene expression, leveraging the shared regulatory architecture of tissues. This method enhances our understanding of coordinated biological mechanisms involved in disease and homeostasis.
NATURE MACHINE INTELLIGENCE
(2023)
Article
Biochemistry & Molecular Biology
Bo Wang, Shahab Razavi, Eric R. Gamazon
Summary: Deep Mutational Scanning (DMS) allows for the measurement of mutational effects on protein properties with high resolution. In this study, deep learning is applied to model the mutational effects of the Alzheimer's Disease associated peptide A beta 42 on aggregation-related biochemical traits. Neural network architectures such as Convolutional Neural Networks and Recurrent Neural Networks are found to be effective models, even with limited data. The study demonstrates the potential of neural network derived sequence-phenotype mapping in protein engineering and therapeutic design.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Cell Biology
Ying Wang, Shinichi Namba, Esteban Lopera, Sini Kerminen, Kristin Tsuo, Kristi Lall, Masahiro Kanai, Wei Zhou, Kuan-Han Wu, Marie-Julie Fave, Laxmi Bhatta, Philip Awadalla, Ben Brumpton, Patrick Deelen, Kristian Hveem, Valeria Lo Faro, Reedik Magi, Yoshinori Murakami, Serena Sanna, Jordan W. Smoller, Jasmina Uzunovic, Cristen Willer, Eric R. Gamazon, Nancy J. Cox, Ida Surakka, Yukinori Okada, Alicia R. Martin, Jibril Hirbo
Summary: This study utilized data from GBMI to explore methodological considerations and performance of PRS for 14 disease endpoints across global populations. The study provides lessons for PRS construction, evaluation, and interpretation and highlights the importance of PRS in the biobank-scale genomics era.
Article
Biochemical Research Methods
Wanying Zhu, Hung-Hsin Chen, Alexander S. Petty, Lauren E. Petty, Hannah G. Polikowsky, Eric R. Gamazon, Jennifer E. Below, Heather M. Highland
Summary: Combining and handling imputation quality and missing variants in multiple large VCF files in genomic data is challenging. To address this, we developed IMMerge, a Python-based tool that utilizes multiprocessing to reduce running time, and correctly combines imputation quality scores with Fisher's z transformation.