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Lookup NU author(s): Professor Chiara Marini Bettolo, Helen Walker
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. 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.
Author(s): Ibanez K, Jadhav B, Zanovello M, Gagliardi D, Clarkson C, Facchini S, Garg P, Martin-Trujillo A, Gies SJ, Galassi Deforie V, Dalmia A, Hensman Moss DJ, Vandrovcova J, Rocca C, Moutsianas L, Marini-Bettolo C, Walker H, Turner C, Shoai M, Long JD, Fratta P, Langbehn DR, Tabrizi SJ, Caulfield MJ, Cortese A, Escott-Price V, Hardy J, Houlden H, Sharp AJ, Tucci A
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Year: 2024
Pages: ePub ahead of Print
Online publication date: 01/10/2024
Acceptance date: 11/07/2024
Date deposited: 15/10/2024
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41591-024-03190-5
DOI: 10.1038/s41591-024-03190-5
Data Access Statement: For 100K GP, full data are available in the Genomic England Secure Research Environment. Access is controlled to protect the privacy and confidentiality of participants in the Genomics England 100K GP and to comply with the consent given by participants for use of their healthcare and genomic data. Access to full data is permitted through the Research Network (https://www.genomicsengland.co.uk/research/academic/join-research-network). For TOPMed, a detailed description of the TOPMed participant consents and data access is provided in Box 1 of ref. 55. TOPMed data used in this manuscript are available through dbGaP. The dbGaP accession numbers for all TOPMed studies referenced in this paper are listed in Supplementary Table 23. [For the full data access statement please see the article.]
PubMed id: 39354197
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