Year: 2024
Type: article
Study design: Observational Study
Abstract: Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions and technological limitations leading to underascertainment. Here, leveraging whole-genome sequencing data from 82,176 individuals from different populations, we found an overall disease allele frequency of REDs of 1 in 283 individuals. Modeling disease prevalence using genetic data, age at onset and survival, we show that the expected number of people with REDs would be two to three times higher than currently reported figures, indicating underdiagnosis and/or incomplete penetrance. While some REDs are population specific, for example, Huntington disease-like 2 in Africans, most REDs are represented in all broad genetic ancestries (that is, Europeans, Africans, Americans, East Asians and South Asians), challenging the notion that some REDs are found only in specific populations. These results have worldwide implications for local and global health communities in the diagnosis and counseling of REDs.
Source: Nature Medicine
Authors: Kristina Ibañez, Bharati Jadhav, Matteo Zanovello, Delia Gagliardi, Christopher Clarkson, Stefano Facchini, Paras Garg, Alejandro Martin-Trujillo, Scott J Gies, Valentina Galassi Deforie, Anupriya Dalmia, Davina J. Hensman Moss, Jana Vandrovcova, Clarissa Rocca, Loukas Moutsianas, Chiara Marini-Bettolo, Helen Walker, Chris Turner, Maryam Shoai, Jeffrey D Long, EUROSCA network, Pietro Fratta, Douglas R Langbehn, Sarah J Tabrizi, Mark J Caulfield, Andrea Cortese, Valentina Escott-Price, John Hardy, Henry Houlden, Andrew J Sharp, Arianna Tucci
Institutions: Queen Mary University of London, William Harvey Research Institute, Icahn School of Medicine at Mount Sinai, UCL Queen Square Institute of Neurology, University College London, UK Dementia Research Institute, St George's, University of London, Genomics England, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle University, National Hospital for Neurology and Neurosurgery, University of Iowa, Cardiff University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Funders: U.S. Department of Health and Human Services, Andrea and Charles Bronfman Philanthropies, Pfizer, AstraZeneca, Women's Health Initiative, Jackson State University, Icahn School of Medicine at Mount Sinai, COPD Foundation, Queen Mary University of London, Sunovion, Wellcome Trust, Broad Institute, UK Research and Innovation, Barts Charity, Mississippi State Department of Health, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, National Institutes of Health, U.S. Food and Drug Administration, Universitätsklinikum Tübingen, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
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OpenAlex ID: W4403039302