Article
Genetics & Heredity
Alison R. Barton, Maxwell A. Sherman, Ronen E. Mukamel, Po-Ru Loh
Summary: This study leveraged haplotype sharing in the UK Biobank to impute exome-wide variants and identified significant associations involving rare protein-altering variants. The research revealed significant associations in multiple genes and proposed allelic series containing multiple "likely-causal" variants.
Article
Genetics & Heredity
Robin J. Hofmeister, Diogo M. Ribeiro, Simone Rubinacci, Olivier Delaneau
Summary: SHAPEIT5, a new phasing method, accurately processes large sequencing datasets and improves imputation accuracy by generating reference panels of haplotypes. The method was applied to UK Biobank data, which resulted in the identification of 549 genes with compound heterozygous loss-of-function events. The use of UK Biobank as a reference panel, coupled with SHAPEIT5 phasing, further enhances genotype imputation accuracy.
Article
Clinical Neurology
Junyu Liu, Xin Liao, Jilin Zhou, Bingyang Li, Lu Xu, Songlin Liu, Yifeng Li, Dun Yuan, Chongyu Hu, Weixi Jiang, Junxia Yan
Summary: Intracranial aneurysm is a cerebrovascular disorder characterized by abnormal dilation of blood vessels due to weakening of the blood vessel wall, which can result in serious complications. The study identified ANK3 gene as highly related to IA, influencing the migration of vascular endothelial cells and cell-cell connections, and potentially accelerating aneurysm formation.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Fahri Kucukali, Alexander Neumann, Jasper Van Dongen, Tim De Pooter, Geert Joris, Peter De Rijk, Olena Ohlei, Valerija Dobricic, Isabelle Bos, Stephanie J. B. Vos, Sebastiaan Engelborghs, Ellen De Roeck, Rik Vandenberghe, Silvy Gabel, Karen Meersmans, Magda Tsolaki, Frans Verhey, Pablo Martinez-Lage, Mikel Tainta, Giovanni Frisoni, Oliver Blin, Jill C. Richardson, Regis Bordet, Philip Scheltens, Julius Popp, Gwendoline Peyratout, Peter Johannsen, Lutz Frolich, Yvonne Freund-Levi, Johannes Streffer, Simon Lovestone, Cristina Legido-Quigley, Mara Ten Kate, Frederik Barkhof, Henrik Zetterberg, Lars Bertram, Mojca Strazisar, Pieter Jelle Visser, Christine Van Broeckhoven, Kristel Sleegers
Summary: In this study, the association between rare genetic variation and AD-related biomarker traits was investigated. Several novel gene-trait associations were identified, shedding light on the role of rare coding variation in the pathophysiological processes of AD.
ALZHEIMERS & DEMENTIA
(2022)
Article
Medicine, General & Internal
Uyenlinh L. Mirshahi, Jung Kim, Ana F. Best, Zongming E. Chen, Ying Hu, Jeremy S. Haley, Alicia Golden, Richard Stahl, Kandamurugu Manickam, Ann G. Carr, Laura A. Harney, Amanda Field, Jessica Hatton, Kris Ann P. Schultz, Andrew J. Bauer, D. Ashley Hill, Philip S. Rosenberg, Michael F. Murray, David J. Carey, Douglas R. Stewart
Summary: Genetic mutations in DICER1 are associated with increased risks of rare and common neoplasms and thyroid disease. This study found that germline DICER1 pLOF variants were more prevalent in the population than expected, and were significantly associated with risks of thyroid cancer. The genome-first approach may be an efficient method for risk estimation in clinical cohorts.
Article
Biology
Xu Jingxiong, Xu Wei, Laurent Briollais
Summary: A novel statistical approach based on Bayes Factor was proposed for evaluating the association between rare genetic variants and disease outcomes, with Bayesian control of false Discovery Rate for genome-wide inference. Simulation studies showed the new BF statistic outperformed standard methods in case-control studies with moderate sample sizes. The real data application in a lung cancer case-control study found enrichment for RVs in known and novel cancer genes, and using informative prior improved gene discovery compared to noninformative prior.
Article
Cell Biology
Raffaele Gaeta, Alberto Righi, Marco Gambarotti, Paolo Aretini, Francesca Lessi, Chiara Maria Mazzanti, Irene Mancini, Pamela Pinzani, Beatrice Belgio, Marta Sbaraglia, Angelo Paolo Dei Tos, Alessandro Franchi
Summary: This study examined the clinicopathological, immunohistochemical, and molecular features of six cases of chondroblastoma-like osteosarcoma (CBLOS). The results showed that CBLOS has different genetic characteristics and a less aggressive clinical behavior compared to conventional high-grade osteosarcoma (CHGOS).
Article
Anesthesiology
Xiang Ao, Marc Parisien, Maha Zidan, Audrey V. V. Grant, Amy E. E. Martinsen, Bendik S. S. Winsvold, Luda Diatchenko
Summary: This study conducted gene-based rare variant analyses on 200,000 human subjects in the UK biobank whole-exome sequencing database to investigate different chronic pain states. The results identified the SLC13A1 gene as associated with various chronic pain conditions and highlighted its importance in sulfate homeostasis in the nervous system. These findings suggest new therapeutic approaches for personalized treatment of chronic pain, especially in individuals with mutations in the SLC13A1 gene.
Article
Genetics & Heredity
Elisabetta Flex, Valentina Imperatore, Giovanna Carpentieri, Alessandro Bruselles, Andrea Ciolfi, Simone Pizzi, Maria Giovanna Tedesco, Daniela Rogaia, Amedea Mencarelli, Giuseppe Di Cara, Alberto Verrotti, Stefania Troiani, Giuseppe Merla, Marco Tartaglia, Paolo Prontera
Summary: A rare form of brachyolmia associated with AI has been identified as a new nosologic entity, characterized by skeletal dysplasia and severe enamel and dental anomalies. Pathogenic variants in LTBP3 have been implicated in the pathogenesis of this disorder, identified in less than 10 families. This study further supports the idea that brachyolmia with AI is a distinct disease entity with LTBP3 variations playing a role in its development.
Article
Clinical Neurology
Daniel G. Calame, Jawid M. Fatih, Isabella Herman, Zeynep Coban-Akdemir, Haowei Du, Tadahiro Mitani, Shalini N. Jhangiani, Dana Marafi, Richard A. Gibbs, Jennifer E. Posey, Vidya P. Mehta, Carrie A. Mohila, Farida Abid, Timothy E. Lotze, Davut Pehlivan, Adekunle M. Adesina, James R. Lupski
Summary: Exome sequencing has transformed rare disease management, but the quality of phenotypic data remains a limiting factor in achieving molecular diagnoses. Deep clinicopathological phenotyping can enhance diagnostic yield and have significant implications for clinical practice. This case study demonstrates the value of integrating clinicopathologic data into exome sequencing analysis for improved molecular diagnosis.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Cell Biology
Kerstin Jurk, Anke Adenaeuer, Stefanie Sollfrank, Kathrin Gross, Friederike Haeuser, Andreas Czwalinna, Josef Erkel, Nele Fritsch, Dana Marandiuc, Martin Schaller, Karl J. Lackner, Heidi Rossmann, Frauke Bergmann
Summary: In this study, a novel GATA1 missense variant was detected in a male patient and his daughter, causing moderate bleeding diathesis and platelet abnormalities. The dysfunction of GATA1 also had mild effects on erythrocytes. Additionally, a mild SLC4A1 defect may contribute to spherocytosis and hemolysis in the daughter.
Article
Pediatrics
Xinping Zhang, Xiayan Kang, Meiyu Yang, Zili Cai, Yulei Song, Xiong Zhou, Jianshe Cao, Chengjuan Wang, Kang Huang, Yani Peng, Jie He, Zhenghui Xiao
Summary: This study identified a novel homozygous variant in the RAG1 gene that causes severe combined immunodeficiency (SCID). This finding expands the variant spectrum of RAG1 in SCID and provides further evidence for the clinical diagnosis of SCID.
Article
Genetics & Heredity
Tianyuan Lu, Sirui Zhou, Haoyu Wu, Vincenzo Forgetta, Celia M. T. Greenwood, J. Brent Richards
Summary: Rare pathogenic variants are more prevalent among affected patients with a low PRS. Therefore, prioritizing individuals with disease but low PRS for sequencing may increase the yield of sequencing studies to identify rare variant heterozygotes.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
He Li, Moez Dawood, Michael M. Khayat, Jesse R. Farek, Shalini N. Jhangiani, Ziad M. Khan, Tadahiro Mitani, Zeynep Coban-Akdemir, James R. Lupski, Eric Venner, Jennifer E. Posey, Aniko Sabo, Richard A. Gibbs
Summary: This study evaluated the impact of using different reference assemblies on the identification of variants associated with rare and common diseases from large-scale exome-sequencing data. The results showed that using different references led to approximately 1.5% discordance in SNVs and 2.0% discordance in indels. The discordant variants were mainly clustered within discrete discordant reference patches enriched for specific genomic elements.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Na Zhu, Emilia M. Swietlik, Carrie L. Welch, Michael W. Pauciulo, Jacob J. Hagen, Xueya Zhou, Yicheng Guo, Johannes Karten, Divya Pandya, Tobias Tilly, Katie A. Lutz, Jennifer M. Martin, Carmen M. Treacy, Erika B. Rosenzweig, Usha Krishnan, Anna W. Coleman, Claudia Gonzaga-Juaregui, Allan Lawrie, Richard C. Trembath, Martin R. Wilkins, Nicholas W. Morrell, Yufeng Shen, Stefan Graf, William C. Nichols, Wendy K. Chung
Summary: The study identified seven genes with rare deleterious variants associated with IPAH, including three known genes and two new candidate genes; analysis of pediatric IPAH showed a significant burden of de novo variants, with at least eight novel candidate genes related to lung/heart development.
Article
Endocrinology & Metabolism
Katia K. Mattis, Nicole A. J. Krentz, Christoph Metzendorf, Fernando Abaitua, Aliya F. Spigelman, Han Sun, Jennifer M. Ikle, Swaraj Thaman, Antje K. Rottner, Austin Bautista, Eugenia Mazzaferro, Marta Perez-Alcantara, Jocelyn E. Manning E. Fox, Jason M. Torres, Agata Wesolowska-Andersen, Grace Z. Z. Yu, Anubha Mahajan, Anders Larsson, Patrick E. MacDonald, Benjamin Davies, Marcel den Hoed, Anna L. Gloyn
Summary: Genome-wide studies have identified multiple signals at the RREB1 locus associated with type 2 diabetes risk and glycaemic traits. However, the function of RREB1 in glucose homeostasis and its impact on diabetes risk are poorly understood. This study used zebrafish and human beta cell models to investigate the role of RREB1 in pancreatic endocrine cell development and function. The results suggest that RREB1 regulates beta cell function by transcriptionally regulating genes involved in beta cell development and function.
Article
Genetics & Heredity
Antje K. Rottner, Yingying Ye, Elena Navarro-Guerrero, Varsha Rajesh, Alina Pollner, Romina J. Bevacqua, Jing Yang, Aliya F. Spigelman, Roberta Baronio, Austin Bautista, Soren K. Thomsen, James Lyon, Sameena Nawaz, Nancy Smith, Agata Wesolowska-Andersen, Jocelyn E. Manning Fox, Han Sun, Seung K. Kim, Daniel Ebner, Patrick E. MacDonald, Anna L. Gloyn
Summary: Through a genome-wide CRISPR loss-of-function screen, we identified 580 genes associated with type 2 diabetes (T2D) and found 20 candidate transcripts, including the autophagy receptor CALCOCO2, which were supported by genetic and genomic data. Loss of CALCOCO2 led to distorted mitochondria, accumulation of immature proinsulin-containing granules, and autophagosome accumulation upon late-stage autophagy inhibition. Carriers of T2D-associated CALCOCO2 variants also showed altered insulin secretion.
Article
Genetics & Heredity
Eleanor Wong, Nicolas Bertin, Maxime Hebrard, Roberto Tirado-Magallanes, Claire Bellis, Weng Khong Lim, Chee Yong Chua, Philomena Mei Lin Tong, Raymond Chua, Kenneth Mak, Tit Meng Lim, Wei Yang Cheong, Kwee Eng Thien, Khean Teik Goh, Jin-Fang Chai, Jimmy Lee, Joseph Jao-Yiu Sung, Tien Yin Wong, Calvin Woon Loong D. Chin, Peter Gluckman, Liuh Ling Goh, Kenneth Hon Kim Ban, Tin Wee M. Tan, Rob M. Van Dam, Yik Ying Teo, Marie Loh, Paul Eillot, Eng Sing Lee, Joanne Ngeow, Elio Riboli, Rinkoo Dalan, Irfahan Kassam, Lakshmi Narayanan Lakshmanan, Tock Han Lim, Hong Kiat Ng, Theresia Mina, Darwin Tay, Charumathi Sabanayagam, Yih Chung Tham, Tyler Rim, Tin Aung, Miao Ling Chee, Hengtong Li, Miao Li Chee, Khung Keong Yeo, Stuart Alexander Cook, Chee Jian Pua, Chengxi Yang, Yap Seng Chong, Johan Gunnar Eriksson, Kok Hian Tan, Fabian Yap, Chia Wei Lim, Pi Kuang Tsai, Wen Jie Chew, Wey Ching Sim, Li-xian Grace Toh, Clarabelle Bitong Lin, Yee Yen Sia, Tat Hung Koh, Wee Yang Meah, Joanna Hui Juan Tan, Justin Jeyakani, Jack Ow, Shimin Ang, Ashar J. Malik, Dimitar Kenanov, Xueling Sim, Ching-Yu Cheng, Sonia Davila, Neerja Karnani, Khai Pang Leong, Jianjun Liu, Shyam Prabhakar, Sebastian Maurer-Stroh, Chandra Shekhar Verma, Pavitra Krishnaswamy, Rick Siow Mong Goh, Irenaeus Chia, Clarissa Ho, Doreen Low, Suchin Virabhak, Jacklyn Yong, Weiling Zheng, Shih Wee Seow, Yee Kwang Seck, Mingshi Koh, John C. Chambers, E. Shyong Tai, Patrick Tan
Summary: This article discusses Singapore's efforts to establish a National Precision Medicine Strategy by integrating genomic, clinical, and lifestyle data of up to one million individuals. Precision medicine has the potential to revolutionize healthcare by detecting diseases early, refining diagnoses, and tailoring treatments for groups and individuals. The lack of representation of Asian ancestries in existing genomic-phenotypic databases presents a missed opportunity for new discoveries, especially for diseases relevant to these populations. The Singapore National Precision Medicine initiative aims to generate integrated data from various sources over a 10-year period, including genomic, lifestyle, health, social, and environmental data, in order to promote precision medicine adoption and address social, ethical, legal, and regulatory challenges.
Article
Food Science & Technology
Dimeng Yang, Huey Lee Lew, Ying Yuan Mak, Sean Jun Leong Ou, Jie Ai Lim, Yuyun Lu, Cassandra Li Yi Seah, Magdalene Qiao Hui Tan, Dejian Huang, E. Shyong Tai, Mei Hui Liu
Summary: This study investigated the use of freeze-dried okra seed flour (OSF) as a functional ingredient to lower the glycemic index (GI) of rice noodles and attenuate postprandial blood glucose rise. The results showed that 20% okra seed fortified noodles significantly reduced postprandial glucose and insulin peaks compared to the control noodles. The addition of OSF also increased satiety and did not affect gut hormone responses.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Biology
Anthony M. Musolf, Annechien E. G. Haarman, Robert N. Luben, Jue-Sheng Ong, Karina Patasova, Rolando Hernandez Trapero, Joseph Marsh, Ishika Jain, Riya Jain, Paul Zhiping Wang, Deyana D. Lewis, Milly S. Tedja, Adriana I. Iglesias, Hengtong Li, Cameron S. Cowan, Ginevra Biino, Alison P. Klein, Priya Duggal, David A. Mackey, Caroline Hayward, Toomas Haller, Andres Metspalu, Juho Wedenoja, Olavi Parssinen, Ching-Yu Cheng, Seang-Mei Saw, Dwight Stambolian, Pirro G. Hysi, Anthony P. Khawaja, Veronique Vitart, Christopher J. Hammond, Cornelia M. van Duijn, Virginie J. M. Verhoeven, Caroline C. W. Klaver, Joan E. Bailey-Wilson
Summary: Refractive error is a complex eye condition caused by genetic and environmental factors. Genome-wide association studies have identified common genetic risk factors, but a significant portion of the heritability is still unexplained. By conducting gene-based association tests, we identified 129 unique genes associated with refractive error in a large dataset. Some of the novel candidates, such as PDCD6IP, PER3, and P4HTM, show promise for future functional studies and validation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Maria C. Costanzo, Marcin von Grotthuss, Jeffrey Massung, Dongkeun Jang, Lizz Caulkins, Ryan Koesterer, Clint Gilbert, Ryan P. Welch, Parul Kudtarkar, Quy Hoang, Andrew P. Boughton, Preeti Singh, Ying Sun, Marc Duby, Annie Moriondo, Trang Nguyen, Patrick Smadbeck, Benjamin R. Alexander, MacKenzie Brandes, Mary Carmichael, Peter Dornbos, Todd Green, Kenneth C. Huellas-Bruskiewicz, Yue Ji, Alexandria Kluge, Aoife C. McMahon, Josep M. Mercader, Oliver Ruebenacker, Sebanti Sengupta, Dylan Spalding, Daniel Taliun, Philip Smith, Melissa K. Thomas, Beena Akolkar, M. Julia Brosnan, Andriy Cherkas, Audrey Y. Chu, Eric B. Fauman, Caroline S. Fox, Tania Nayak Kamphaus, Melissa R. Miller, Lynette Nguyen, Afshin Parsa, Dermot F. Reilly, Hartmut Ruetten, David Wholley, Norann A. Zaghloul, Goncalo R. Abecasis, David Altshuler, Thomas M. Keane, Mark I. McCarthy, Kyle J. Gaulton, Jose C. Florez, Michael Boehnke, Noel P. Burtt, Jason Flannick
Summary: This study aims to make the Type 2 Diabetes Knowledge Portal (T2DKP) more accessible and useful to both new and existing users. It evaluates the comprehensiveness of T2DKP by comparing its datasets with other repositories, guides researchers unfamiliar with human genetic data on how to interpret and use the data through T2DKP, and discusses the importance of democratizing access to complex disease genetic results.
Article
Biochemistry & Molecular Biology
Elizabeth M. Humphries, Kwangmi Ahn, Rachel L. Kember, Fabiana L. Lopes, Evelina Mocci, Juan M. Peralta, John Blangero, David C. Glahn, Fernando S. Goes, Peter P. Zandi, Peter Kochunov, Cristopher Van Hout, Alan R. Shuldiner, Toni I. Pollin, Braxton D. Mitchell, Maja Bucan, L. Elliot Hong, Francis J. McMahon, Seth A. Ament
Summary: By conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish, four significant risk loci were identified, all of which were associated with more than a 2-fold relative risk. Further assessments revealed effects of these risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that these risk loci may harbor novel risk-associated genes, which interact with known neuropsychiatry-associated genes through gene interaction networks. Annotation of the variants at these risk loci revealed enrichment of non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. These findings provide valuable insights into the genetic architecture of mood disorders and serve as a foundation for mechanistic and clinical studies.
MOLECULAR PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Rosie Clark, Samantha Sze-Yee Lee, Ran Du, Yining Wang, Sander C. M. Kneepkens, Jason Charng, Yu Huang, Michael L. Hunter, Chen Jiang, J. Willem L. Tideman, Ronald B. Melles, Caroline C. W. Klaver, David A. Mackey, Cathy Williams, Helene Choquet, Kyoko Ohno-Matsui, Jeremy A. Guggenheim
Summary: This study aimed to predict the risk of high myopia (HM) through an improved polygenic score (PGS) and test if the PGS is predictive of myopic macular degeneration (MMD) after considering refractive error. The study found that PGS can predict the risk of HM in Europeans, but its predictive ability is weaker in other populations.
Article
Health Care Sciences & Services
Oscar Castro, Jacqueline Louise Mair, Alicia Salamanca-Sanabria, Aishah Alattas, Roman Keller, Shenglin Zheng, Ahmad Jabir, Xiaowen Lin, Bea Franziska Frese, Chang Siang Lim, Prabhakaran Santhanam, Rob M. van Dam, Josip Car, Jimmy Lee, E. Shyong Tai, Elgar Fleisch, Florian von Wangenheim, Lorainne Tudor Car, Falk Mueller-Riemenschneider, Tobias Kowatsch
Summary: This paper describes the development of LvL UP 1.0 & DPRIME, a smartphone-based lifestyle intervention aimed at preventing non-communicable diseases and common mental disorders. The intervention is designed to be scalable and engaging, and it incorporates components such as health literacy coaching, daily activity suggestions, and progress feedback.
FRONTIERS IN DIGITAL HEALTH
(2023)
Article
Biochemistry & Molecular Biology
Deirdre K. Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L. Benham, Dhanasekaran Bodhini, Amy L. Clark, Kevin Colclough, Rosa Corcoy, Sara J. Cromer, Daisy Duan, Jamie L. Felton, Ellen C. Francis, Pieter Gillard, Veronique Gingras, Romy Gaillard, Eram Haider, Alice Hughes, Jennifer M. Ikle, Laura M. Jacobsen, Anna R. Kahkoska, Jarno L. T. Kettunen, Raymond J. Kreienkamp, Lee-Ling Lim, Jonna M. E. Mannisto, Robert Massey, Niamh-Maire Mclennan, Rachel G. Miller, Mario Luca Morieri, Jasper Most, Rochelle N. Naylor, Bige Ozkan, Kashyap Amratlal Patel, Scott J. Pilla, Katsiaryna Prystupa, Sridharan Raghavan, Mary R. Rooney, Martin Schoen, Zhila Semnani-Azad, Magdalena Sevilla-Gonzalez, Pernille Svalastoga, Wubet Worku Takele, Claudia Ha-ting Tam, Anne Cathrine B. Thuesen, Mustafa Tosur, Amelia S. Wallace, Caroline C. Wang, Jessie J. Wong, Jennifer M. Yamamoto, Katherine Young, Chloe Amouyal, Mette K. Andersen, Maxine P. Bonham, Mingling Chen, Feifei Cheng, Tinashe Chikowore, Sian C. Chivers, Christoffer Clemmensen, Dana Dabelea, Adem Y. Dawed, Aaron J. Deutsch, Laura T. Dickens, Linda A. DiMeglio, Monika Dudenhoffer-Pfeifer, Carmella Evans-Molina, Maria Merce Fernandez-Balsells, Hugo Fitipaldi, Stephanie L. Fitzpatrick, Stephen E. Gitelman, Mark O. Goodarzi, Jessica A. Grieger, Marta Guasch-Ferre, Nahal Habibi, Torben Hansen, Chuiguo Huang, Arianna Harris-Kawano, Heba M. Ismail, Benjamin Hoag, Randi K. Johnson, Angus G. Jones, Robert W. Koivula, Aaron Leong, Gloria K. W. Leung, Ingrid M. Libman, Kai Liu, S. Alice Long, William L. Lowe, Robert W. Morton, Ayesha A. Motala, Suna Onengut-Gumuscu, James S. Pankow, Maleesa Pathirana, Sofia Pazmino, Dianna Perez, John R. Petrie, Camille E. Powe, Alejandra Quinteros, Rashmi Jain, Debashree Ray, Mathias Ried-Larsen, Zeb Saeed, Vanessa Santhakumar, Sarah Kanbour, Sudipa Sarkar, Gabriela S. F. Monaco, Denise M. Scholtens, Elizabeth Selvin, Wayne Huey-Herng Sheu, Cate Speake, Maggie A. Stanislawski, Nele Steenackers, Andrea K. Steck, Norbert Stefan, Julie Stoy, Rachael Taylor, Sok Cin Tye, Gebresilasea Gendisha Ukke, Marzhan Urazbayeva, Bart Van der Schueren, Camille Vatier, John M. Wentworth, Wesley Hannah, Sara L. White, Gechang Yu, Yingchai Zhang, Shao J. Zhou, Jacques Beltrand, Michel Polak, Ingvild Aukrust, Elisa de Franco, Sarah E. Flanagan, Kristin A. Maloney, Andrew McGovern, Janne Molnes, Mariam Nakabuye, Pal Rasmus Njolstad, Hugo Pomares-Millan, Michele Provenzano, Cecile Saint-Martin, Cuilin Zhang, Yeyi Zhu, Sungyoung Auh, Russell de Souza, Andrea J. Fawcett, Chandra Gruber, Eskedar Getie Mekonnen, Emily Mixter, Diana Sherifali, Robert H. Eckel, John J. Nolan, Louis H. Philipson, Rebecca J. Brown, Liana K. Billings, Kristen Boyle, Tina Costacou, John M. Dennis, Jose C. Florez, Anna L. Gloyn, Maria F. Gomez, Peter A. Gottlieb, Siri Atma W. Greeley, Kurt Griffin, Andrew T. Hattersley, Irl B. Hirsch, Marie-France Hivert, Korey K. Hood, Jami L. Josefson, Soo Heon Kwak, Lori M. Laffel, Siew S. Lim, Ruth J. F. Loos, Ronald C. W. Ma, Chantal Mathieu, Nestoras Mathioudakis, James B. Meigs, Shivani Misra, Viswanathan Mohan, Rinki Murphy, Richard Oram, Katharine R. Owen, Susan E. Ozanne, Ewan R. Pearson, Wei Perng, Toni I. Pollin, Rodica Pop-Busui, Richard E. Pratley, Leanne M. Redman, Maria J. Redondo, Rebecca M. Reynolds, Robert K. Semple, Jennifer L. Sherr, Emily K. Sims, Arianne Sweeting, Tiinamaija Tuomi, Miriam S. Udler, Kimberly K. Vesco, Tina Vilsboll, Robert Wagner, Stephen S. Rich, Paul W. Franks
Summary: Precision medicine, as part of contemporary evidence-based medicine, aims to reduce errors and optimize outcomes in medical decisions and health recommendations. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review and highlights opportunities for clinical implementation as well as gaps in knowledge.
Editorial Material
Genetics & Heredity
Kristle Garcia, Anna L. Gloyn
Summary: Juan-Mateu et al. discover that pancreatic islet cells employ a regulatory program, initially found in neurons, which involves alternative splicing of microexons in genes relevant to insulin secretion or diabetes risk.
TRENDS IN GENETICS
(2023)
Article
Multidisciplinary Sciences
Hwee Hui Lau, Nicole A. J. Krentz, Fernando Abaitua, Marta Perez-Alcantara, Jun-Wei Chan, Jila Ajeian, Soumita Ghosh, Yunkyeong Lee, Jing Yang, Swaraj Thaman, Benoite Champon, Han Sun, Alokkumar Jha, Shawn Hoon, Nguan Soon Tan, Daphne Su-Lyn Gardner, Shih Ling Kao, E. Shyong Tai, Anna L. Gloyn, Adrian Kee Keong Teo
Summary: The coding variant of the PAX4 gene is associated with an altered risk of type 2 diabetes in East Asian populations. This study found that individuals carrying the specific allele of PAX4 exhibited decreased pancreatic beta cell function, and a newly identified allele was found in some diabetes patient pedigrees. Knockdown of the PAX4 gene resulted in impaired insulin secretion and altered hormone gene expression in a human beta cell model. In vitro differentiation experiments also showed that cells carrying specific risk alleles exhibited increased polyhormonal endocrine cell formation and decreased insulin content.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Jowy Yi Hoong Seah, Xueling Sim, Chin Meng Khoo, E. Shyong Tai, Rob M. van Dam
Summary: This study compared the risk of type 2 diabetes (T2D) among Chinese, Indian, and Malay ethnic groups and examined the biological factors that contribute to ethnic differences. The results showed that Malays and Indians had approximately twice the risk of T2D compared to Chinese. Higher BMI explained the higher risk for Malays, and factors such as BMI, waist circumference, inflammation, insulin resistance, and high-density lipoprotein cholesterol contributed to the higher risk for Indians. However, part of the higher T2D risk associated with Indian ethnicity remained unexplained. Chinese participants had the lowest adiponectin levels despite their lower diabetes risk.
BMJ OPEN DIABETES RESEARCH & CARE
(2023)
Article
Endocrinology & Metabolism
Ming Yeh Lee, Anna L. Gloyn, David M. Maahs, Priya Prahalad
Summary: Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes. This case study highlights the safe and effective use of continuous glucose monitoring, insulin pump, automated insulin delivery system, and remote patient monitoring for infants with NDM, enabling rapid and safe transition from insulin to oral sulfonylurea and improving glycemia, quality of life, and cost-effectiveness by shortening hospital stay.
CASE REPORTS IN ENDOCRINOLOGY
(2023)
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.