拉丁裔混合人群中阿尔茨海默病和额颞叶痴呆的遗传贡献。
Genetic Contributions to Alzheimer's Disease and Frontotemporal Dementia in Admixed Latin American Populations.
作者信息
Acosta-Uribe Juliana, Escudero Stefanie D Piña, Cochran J Nicholas, Taylor Jared W, Castruita Alejandra, Jonson Caroline, Barinaga Erin A, Roberts Kevin, Levine Alexandra R, George Dawwod S, AvilaFunes José Alberto, Behrens María I, Bruno Martin A, Brusco Luis I, Custodio Nilton, Duran-Aniotz Claudia, Lopera Francisco, Matallana Diana L, Slachevsky Andrea, Takada Leonel T, Zapata-Restrepo Lina M, Durón-Reyes Dafne E, Resende Elisa de Paula França, Gelvez Nancy, Gómez Luisa F, Godoy Maria E, Maito Marcelo A, Avandel Shireen, Miller Bruce L, Nalls Mike A, Leonard Hampton, Vitale Dan, Bandres-Ciga Sara, Koretsky Mathew J, Singleton Andrew B, Pantazis Caroline B, Valcour Victor, Ibañez Agustin, Kosik Kenneth S, Yokoyama Jennifer S, Bistue M Beatriz
出版信息
Res Sq. 2025 May 6:rs.3.rs-5462510. doi: 10.21203/rs.3.rs-5462510/v1.
Latin America's diverse genetic landscape provides a unique opportunity to study Alzheimer's disease (AD) and frontotemporal dementia (FTD). The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) recruited 2,162 participants with AD, FTD, or as healthy controls from six countries: Argentina, Brazil, Chile, Colombia, Mexico, and Peru. Participants underwent genomic sequencing and population structure analyses were conducted using Principal Component Analysis and ADMIXTURE. The study revealed a predominant mix of American, African, and European ancestries, with an additional East Asian component in Brazil. Variant curation identified 17 pathogenic variants, pathogenic expansion, and 44 variants of uncertain significance. Seventy families showed autosomal dominant inheritance, with 48 affected by AD and 22 by FTD. This represents the first large-scale genetic study of AD and FTD in Latin America, highlighting the need to consider diverse ancestries, social determinants of health, and cultural factors when assessing genetic risk for neurodegenerative diseases.
拉丁美洲多样的基因格局为研究阿尔茨海默病(AD)和额颞叶痴呆(FTD)提供了独特的机会。拉丁美洲扩大痴呆症研究多伙伴联盟(ReDLat)从阿根廷、巴西、智利、哥伦比亚、墨西哥和秘鲁六个国家招募了2162名患有AD、FTD或作为健康对照的参与者。参与者接受了基因组测序,并使用主成分分析和ADMIXTURE进行了群体结构分析。该研究揭示了美洲、非洲和欧洲血统的主要混合,在巴西还有额外的东亚成分。变异筛选确定了17个致病变异、致病扩增和44个意义未明的变异。70个家庭显示常染色体显性遗传,其中48个受AD影响,22个受FTD影响。这是拉丁美洲首次对AD和FTD进行的大规模基因研究,强调了在评估神经退行性疾病的遗传风险时需要考虑不同的血统、健康的社会决定因素和文化因素。