Article
Endocrinology & Metabolism
Tianyuan Lu, Vincenzo Forgetta, Sirui Zhou, J. Brent Richards, Celia M. T. Greenwood
Summary: Research has found that rare genetic determinants may assist in predicting fracture risk among individuals carrying influential rare variants. However, in population-level risk screening, the predictive performance of rare genetic determinants is not better than common genetic determinants.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Hematology
Antoine Rimbert, Xavier Vanhoye, Dramane Coulibaly, Marie Marrec, Matthieu Pichelin, Sybil Charriere, Noel Peretti, Rene Valero, Matthieu Wargny, Alain Carrie, Pierre Lindenbaum, Jean-Francois Deleuze, Emmanuelle Genin, Richard Redon, Pierre Antoine Rollat-Farnier, Didier Goxe, Gilles Degraef, Oriane Marmontel, Eleonore Divry, Edith Bigot-Corbel, Philippe Moulin, Bertrand Cariou, Mathilde Di Filippo
Summary: This study compared hepatic alterations in monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause, finding that monogenic hypobetalipoproteinemia is associated with a higher risk of liver abnormalities compared to polygenic hypobetalipoproteinemia.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Oncology
Hui-Qi Qu, John J. Connolly, Peter Kraft, Jirong Long, Alexandre Pereira, Christopher Flatley, Constance Turman, Bram Prins, Frank Mentch, Paulo A. Lotufo, Per Magnus, Meir J. Stampfer, Rulla Tamimi, A. Heather Eliassen, Wei Zheng, Gun Peggy Stromstad Knudsen, Oyvind S. Helgeland, Adam Butterworth, Hakon M. Hakonarson, Patrick Sleiman
Summary: Through the collaboration model of IHCC, a globally applicable trans-ethnic PRS for BMI was developed, which can effectively estimate an individual's risk of developing complex traits such as obesity.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Victor Nauffal, Valerie N. Morrill, Sean J. Jurgens, Seung Hoan Choi, Amelia W. Hall, Lu-Chen Weng, Jennifer L. Halford, Christina Austin-Tse, Christopher M. Haggerty, Stephanie L. Harris, Eugene K. Wong, Alvaro Alonso, Dan E. Arking, Emelia J. Benjamin, Eric Boerwinkle, Yuan- Min, Adolfo Correa, Brandon K. Fornwalt, Susan R. Heckbert, Charles Kooperberg, Henry J. Lin, Ruth J.f. Loos, Kenneth M. Rice, Namrata Gupta, Thomas W. Blackwell, Braxton D. Mitchell, Alanna C. Morrison, Bruce M. Psaty, Wendy S. Post, Susan Redline, Heidi L. Rehm, Stephen S. Rich, Jerome I. Rotter, Elsayed Z. Soliman, Nona Sotoodehnia, Kathryn L. Lunetta, Patrick T. Ellinor, Steven A. Lubitz
Summary: Using data from large-scale biorepositories, this study found 54 independent loci associated with cardiac repolarization, including 21 novel loci. The findings suggest that both rare variants in genes underlying cardiac repolarization and polygenic risk play a role in determining the duration of QT interval in the population.
Editorial Material
Genetics & Heredity
Clement A. Adebamowo, Adebowale Adeyemo, Adeyinka Ashaye, Onoja M. Akpa, Tinashe Chikowore, Ananyo Choudhury, Yasmina J. Fakim, Segun Fatumo, Neil Hanchard, Michael Hauser, Braxton Mitchell, Nicola Mulder, Solomon F. Ofori-Acquah, Mayowa Owolabi, Michele Ramsay, Bamidele Tayo, Archana Bhavani VasanthKumar, Yuji Zhang, Sally N. Adebamowo
Summary: The CARDINAL study site is a well-powered resource that aims to develop, refine, and validate methods for researching polygenic risk scores, taking into account local ancestry, to improve risk prediction in diverse populations.
Article
Clinical Neurology
Jiangming Sun, Yan Borne, Andreas Edsfeldt, Yunpeng Wang, Mengyu Pan, Olle Melander, Gunnar Engstrom, Isabel Goncalves
Summary: This study examines the prognostic and causal roles of mood disorders in strokes. The findings suggest that genetic susceptibilities for mood disorders are associated with increased risk of strokes, and mood disorders have a causal effect on stroke. This can help identify high-risk women early in life and prevent mood disorders and strokes.
Article
Genetics & Heredity
Tianyuan Lu, Vincenzo Forgetta, John Brent Richards, Celia M. T. Greenwood
Summary: The study aimed to evaluate the usefulness of polygenic risk scores in addition to family history for identifying monogenic causes of complex diseases through deep-depth diagnostic sequencing. The results showed that polygenic risk scores could help identify individuals with monogenic causes among those with a family history, reducing the need for sequencing.
GENETICS IN MEDICINE
(2022)
Article
Pathology
Fujiao Duan, Ling Liu, Xiaolin Chen, Qian Yang, Yiran Wang, Yaodong Zhang, Kaijuan Wang
Summary: This study aimed to identify common variants and lncRNA SNPs associated with gastric cancer risk and construct prediction models based on PRS. The best-fitting model combined PRS with lncRNA SNPs, H. pylori infection, smoking, and drinking, and had optimal predictive ability for gastric cancer risk, helpful for identifying high-risk groups.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2023)
Article
Biology
Tianyuan Lu, Vincenzo Forgetta, J. Brent Richards, Celia M. T. Greenwood
Summary: This study developed a latent factor model to quantify trait heritability beyond what is captured by a common variant-based polygenic risk score, and incorporated family history into genetic risk prediction models, leading to improved risk prediction accuracy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jonathan L. Hess, Daniel S. Tylee, Manuel Mattheisen, Anders D. Borglum, Thomas D. Als, Jakob Grove, Thomas Werge, Preben Bo Mortensen, Ole Mors, Merete Nordentoft, David M. Hougaard, Jonas Byberg-Grauholm, Marie Baekvad-Hansen, Tiffany A. Greenwood, Ming T. Tsuang, David Curtis, Stacy Steinberg, Engilbert Sigurdsson, Hreinn Stefansson, Kari Stefansson, Howard J. Edenberg, Peter Holmans, Stephen Faraone, Stephen J. Glatt
Summary: This study proposed a theoretical framework based on genetic variations that promote resilience to highly heritable polygenic disorders, such as schizophrenia. By establishing a procedure to identify unaffected individuals with relatively high polygenic risk for the disease and generating the first known polygenic resilience score, this work laid a foundation for finding resilience variants for any complex, heritable disorder.
MOLECULAR PSYCHIATRY
(2021)
Article
Ophthalmology
Owen M. Siggs, Xikun Han, Ayub Qassim, Emmanuelle Souzeau, Shilpa Kuruvilla, Henry N. Marshall, Sean Mullany, David A. Mackey, Alex W. Hewitt, Puya Gharahkhani, Stuart MacGregor, Jamie E. Craig
Summary: Both monogenic and high polygenic risk are associated with more than a 2.5-fold increased odds of developing glaucoma and have an equivalent mean age at glaucoma diagnosis, with high polygenic risk being more than 15 times more common in the general population.
JAMA OPHTHALMOLOGY
(2021)
Review
Genetics & Heredity
Xi Cheng, Fengzhou Du, Xiao Long, Jiuzuo Huang
Summary: This article provides an overview of the genetic inheritance model of non-syndromic cleft lip with or without palate (NSCL/P), including both monogenic and polygenic perspectives. Representative genes and regions are presented, along with existing association studies and corresponding loci in the Chinese population. The potential of using polygenic risk scores for risk stratification of NSCL/P is highlighted, offering promising avenues for improved risk assessment and personalized interventions.
Article
Genetics & Heredity
Tianyuan Lu, Vincenzo Forgetta, J. Brent Richards, Celia M. T. Greenwood
Summary: Genomic risk prediction is a promising avenue for personalized medicine, but its accuracy varies among individuals. In this study, researchers constructed polygenic risk scores for 15 physiological and biochemical traits using data from the UK Biobank. They identified 185 genetic loci associated with variability in polygenic prediction for 11 traits. The researchers found that these loci had more complex genetic effects compared to risk loci identified in genome-wide association studies. Incorporating these effects improved the accuracy of polygenic risk scores for certain traits.
Review
Peripheral Vascular Disease
Erin Jacob, Robert A. Hegele
Summary: Patients with polygenic hypercholesterolemia have less severe clinical features compared to monogenic hypercholesterolemia patients but still have a high cardiovascular risk.
CURRENT ATHEROSCLEROSIS REPORTS
(2022)
Article
Immunology
Thomas Clarke, Pan Du, Satyendra Kumar, Shinji L. Okitsu, Mark Schuette, Qi An, Jinyang Zhang, Evgeni Tzvetkov, Mark A. Jensen, Timothy B. Niewold, Elise M. N. Ferre, Julie Nardone, Michail S. Lionakis, Jaromir Vlach, Julie DeMartino, Andrew T. Bender
Summary: Autoimmune diseases can vary in the pattern and range of autoantibodies produced, and these differences may be caused by various breaks in tolerance. By comparing three different autoimmune diseases, APECED, SLE, and SjS, researchers gained insights into the triggers of autoimmunity. APECED was found to have a focused set of shared anti-cytokine antibodies, while SLE had broader autoantibody repertoires targeting mostly intracellular antigens. SjS patients showed few specific autoantibodies, with the highest reactivity against Ro-52 and La. These findings suggest different mechanisms driving autoimmunity in monogenic and polygenic disorders.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Health Care Sciences & Services
Sabe Sabesan, Marie Malica, Chantal Gebbie, Clare Scott, David Thomas, John Zalcberg
Summary: This paper describes the steps and processes involved in the development and implementation of the Australasian Teletrial Model (ATM) by the Clinical Oncology Society of Australia. The implementation of ATM has improved access to clinical trials for patients in regional and rural areas, and enhanced collaboration between metropolitan and regional sites.
JOURNAL OF TELEMEDICINE AND TELECARE
(2023)
Article
Genetics & Heredity
Na Li, Magnus Zethoven, Simone McInerny, Eliza Healey, Dilanka DeSilva, Lisa Devereux, Rodney J. Scott, Paul A. James, Ian G. Campbell
Summary: PALB2 is the most important contributor to familial breast cancer after BRCA1 and BRCA2. This study shows that a clinically important proportion of PALB2 pathogenic mutations in Australian patients with familial breast cancer are large genomic rearrangements (LGRs).
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Steven Attia, Vanessa Bolejack, Kristen N. Ganjoo, Suzanne George, Mark Agulnik, Daniel Rushing, Elizabeth T. Loggers, Michael B. Livingston, Jennifer Wright, Sant P. Chawla, Scott H. Okuno, Denise K. Reinke, Richard F. Riedel, Lara E. Davis, Christopher W. Ryan, Robert G. Maki
Summary: This study reported the preliminary efficacy and toxicity of regorafenib in Ewing family sarcomas. The results showed that regorafenib had modest inhibitory activity against Ewing family sarcomas, with toxicity consistent with that observed in other studies.
Article
Oncology
Belle W. X. Lim, Na Li, Sakshi Mahale, Simone M. McInerny, Magnus Zethoven, Simone M. Rowley, Joanne Huynh, Theresa Wang, Jue Er Amanda Lee, Mia Friedman, Lisa Devereux, Rodney J. Scott, Erica K. Sloan, Paul A. James, Ian G. Campbell
Summary: This study found that BARD1 and RAD51D behave as classic BRCA-like predisposition genes with biallelic loss in breast cancer. In contrast to other breast cancer-related genes, CHEK2 gene lacks biallelic loss, but this does not definitively exclude its involvement in breast cancer predisposition.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Oncology
Philip Heesen, Gabriela Studer, Beata Bode, Hubi Windegger, Benjamin Staeheli, Paul Aliu, Javier Martin-Broto, Alessandro Gronchi, Jean-Yves Blay, Axel Le Cesne, Bruno Fuchs
Summary: This article presents a comprehensive analysis of quality indicators for sarcoma care and introduces a novel interoperable digital platform that gathers information from physicians and patients consecutively and instantly. The platform provides evidence of care quality by analyzing real-time world information, enabling predictive modeling and value-based health care. The lack of global data harmonization and quality standards, as well as discipline, institution, and network fragmentation, hinder the progress in sarcoma care. To improve quality, a common definition of quality indicators and the assessment of longitudinal real-time data are required. An international advisory board defined six categories of quality indicators, which were programmed into the digital platform for analysis and visualization. Standardized quality indicators and their real-time assessment are critical to improving the quality of sarcoma care.
Article
Oncology
Elodie Darbo, Gaelle Perot, Lucie Darmusey, Sophie Le Guellec, Laura Leroy, Laetitia Gaston, Nelly Desplat, Noemie Thebault, Candice Merle, Philippe Rochaix, Thibaud Valentin, Gwenael Ferron, Christine Chevreau, Binh Bui, Eberhard Stoeckle, Dominique Ranchere-Vince, Pierre Meeus, Philippe Terrier, Sophie Piperno-Neumann, Francoise Collin, Gonzague De Pinieux, Florence Duffaud, Jean-Michel Coindre, Jean-Yves Blay, Frederic Chibon
Summary: Leiomyosarcomas are aggressive diseases mainly treated by surgical resection with or without conventional chemotherapy. Two specifically deregulated pathways (MYOCD/SRF and E2F1/RB1) were identified in a subgroup of well-differentiated vascular smooth muscle cell-derived leiomyosarcomas. Targeting the MYOCD/SRF pathway has the potential to be a therapeutic target for leiomyosarcoma.
Article
Genetics & Heredity
Zornitza Stark, Tiffany Boughtwood, Matilda Haas, Jeffrey Braithwaite, Clara L. Gaff, Ilias Goranitis, Amanda B. Spurdle, David P. Hansen, Oliver Hofmann, Nigel Laing, Sylvia Metcalfe, Ainsley J. Newson, Hamish S. Scott, Natalie Thorne, Robyn L. Ward, Marcel E. Dinger, Stephanie Best, Janet C. Long, Sean M. Grimmond, John Pearson, Nicola Waddell, Christopher P. Barnett, Matthew Cook, Michael Field, David Fielding, Stephen B. Fox, Jozef Gecz, Adam Jaffe, Richard J. Leventer, Paul J. Lockhart, Sebastian Lunke, Andrew J. Mallett, Julie McGaughran, Linda Mileshkin, Katia Nones, Tony Roscioli, Ingrid E. Scheffer, Christopher Semsarian, Cas Simons, David M. Thomas, David R. Thorburn, Richard Tothill, Deborah White, Sally Dunwoodie, Peter T. Simpson, Peta Phillips, Marie-Jo Brion, Keri Finlay, Michael CJ. Quinn, Tessa Mattiske, Emma Tudini, Kirsten Boggs, Sean Murray, Kathy Wells, John Cannings, Andrew H. Sinclair, John Christodoulou, Kathryn N. North
Summary: Australian Genomics is a national collaborative partnership that aims to integrate genomics into healthcare through a whole-of-system approach. It has evaluated genomic testing outcomes in over 5,200 individuals across rare disease and cancer studies and provided evidence-based changes in policy and practice, resulting in government funding and access to genomic tests. It has also developed national skills, infrastructure, policy, and data resources to support data sharing and improve clinical genomic delivery.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Patrick Schoffski, Mehdi Lahmar, Anthony Lucarelli, Robert G. Maki
Summary: This article describes an ongoing clinical trial evaluating the efficacy of BI 907828 versus doxorubicin as first-line treatment for advanced DDLPS. The study shows that BI 907828 is able to inhibit the growth of DDLPS and has better efficacy compared to the chemotherapy drug doxorubicin.
Article
Oncology
Gabriella N. Tortorello, Cimarron E. Sharon, Kevin L. L. Ma, Nikhita Perry, Jacob E. Shabason, Robert G. Maki, John T. Miura, Giorgos C. Karakousis
Summary: This study analyzed the use and effectiveness of neoadjuvant chemotherapy (NCT) in high-risk soft tissue sarcoma (STS) patients receiving neoadjuvant radiation therapy (NRT). The results showed that NCT was associated with improved survival, although its usage has decreased over time.
JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Gabriella N. N. Tortorello, Eric H. H. Li, Cimarron E. E. Sharon, Kevin L. L. Ma, Robert G. G. Maki, John T. T. Miura, Douglas L. L. Fraker, Ronald P. P. DeMatteo, Giorgos C. C. Karakousis
Summary: This study analyzed data from 2656 patients with high-grade retroperitoneal sarcoma and found that neoadjuvant chemotherapy did not confer a survival advantage in 5-year overall survival. The authors called for more prospective randomized controlled studies to confirm this finding.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Antony J. Mersiades, Benjamin J. Solomon, David M. Thomas, Chee K. Lee, Michelle M. Cummins, Lucille Sebastian, Mandy L. Ballinger, Emily Collignon, Olivia M. H. Turnbull, Sonia Yip, Rachael L. Morton, Chris Brown, Patrick J. Wheeler, Malinda Itchins, R. John Simes, Nick Pavlakis
Summary: The ASPiRATION study is a national prospective observational cohort study conducted in Australia that aims to assess the feasibility, clinical value, and economic value of comprehensive genomic profiling (CGP) in newly diagnosed metastatic non-squamous non-small-cell lung cancer. The study will enroll 1000 participants and collect clinical outcome data for a minimum of 2 years. The outcomes of the study will describe the ability of CGP to identify actionable genomic alterations, leading to personalized treatment recommendations, and evaluate the feasibility, cost, and utility of implementing CGP nationally. The study is important in advancing the understanding and application of CGP in lung cancer diagnosis and treatment in Australia.
Article
Oncology
Olivier Tredan, Maud Toulmonde, Christophe Le Tourneau, Laure Montane, Antoine Italiano, Isabelle Ray-Coquard, Christelle de la Fouchardiere, Francois Bertucci, Anthony Goncalves, Carlos Gomez-Roca, Benoit You, Valery Attignon, Sandrine Boyault, Philippe A. Cassier, Armelle Dufresne, Severine Tabone-Eglinger, Alain Viari, Emilie Sohier, Maud Kamal, Gwenael Garin, Jean-Yves Blay, David Perol
Summary: Using a randomized discontinuation design, sorafenib was tested on patients with advanced/metastatic solid tumors harboring sorafenib-targeted genes. Continuing sorafenib when stable disease is achieved improves progression-free rate compared to interruption. Sorafenib has tumor-agnostic efficacy in patients with tumors harboring genomic alterations in PDGFRA/B, VEGF-Rs, Flt-3, KIT, FGFR1 or the RAF/MEK/ERK pathway.
Article
Oncology
Xiaolan Feng, Laurie Tonon, Haocheng Li, Elodie Darbo, Erin Pleasance, Nicolas Macagno, Armelle Dufresne, Mehdi Brahmi, Julien Bollard, Francoise Ducimetiere, Marie Karanian, Alexandra Meurgey, Gaelle Perot, Thibaud Valentin, Frederic Chibon, Jean-Yves Blay
Summary: This study is the first comprehensive transcriptomic profiling analysis focused on the tumor immune microenvironment (TIME) in leiomyosarcoma (LMS). The study identified a subset of LMS patients with an active immune microenvironment, which is associated with validated immune signatures observed in other cancers. The study supports the further development of immune biomarkers to select the right LMS patients for immune checkpoint inhibitors (ICIs) in clinical trials.
Article
Oncology
Jocelyn Lippey, Louise Keogh, Ian Campbell, Gregory Bruce Mann, Laura Elenor Forrest
Summary: This study aims to evaluate the impact of the decision aid on women's knowledge, risk perception, acceptance of risk assessment and change of screening frequency, and decision-making. After reviewing the decision aid, there was a significant change in knowledge, acceptance of risk-stratified breast cancer screening and of decreased frequency screening for lower risk. The decision aid has a positive impact on acceptance of lower frequency screening.