Studies in Neuroscience and Complex Systems Unit-CONICET-HEC-UNAJ, Florencio Varela, Argentina.
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Alzheimers Dement. 2024 Feb;20(2):1298-1308. doi: 10.1002/alz.13522. Epub 2023 Nov 20.
Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.
We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population.
We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37-3.63], P = 2.6 × 10 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose.
We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations.
This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.
全基因组关联研究（GWAS）是识别与疾病相关的基因座的基础。然而，它们需要在其他种族中进行复制。
我们对来自阿根廷和智利的 539 名 AD 患者和 854 名对照进行了散发性 AD 的 GWAS。我们将我们的结果与欧洲阿尔茨海默病和痴呆生物银行（EADB）的结果进行了荟萃分析，并在这个混合人群中测试了他们的遗传风险评分（GRS）表现。
我们检测到载脂蛋白 E ε4 是唯一全基因组显著信号（优势比=2.93 [2.37-3.63]，P=2.6×10）。与 EADB 汇总统计数据的荟萃分析显示，有四个新的基因座达到了 GWAS 显著性。这些基因座的功能注释表明了内体/溶酶体功能。最后，AD-GRS 在这些人群中表现出相似的性能，尽管当美洲原住民血统增加时，评分会降低。
我们报告了第一个在南美洲人群中进行的 AD 的 GWAS。它显示了调节欧洲人和这些混合人群 AD 风险的共同遗传因素。
这是在阿根廷和智利人群样本中进行的第一个 AD 全基因组关联研究。跨种族荟萃分析揭示了四个新的基因座，涉及 AD 中的溶酶体功能。这是对 TREM2L、IGH 基因簇和 ADAM17 基因座的首次独立复制。在欧洲人中开发的遗传风险评分（GRS）在该人群中表现良好。美洲原住民血统越高，GRS 值越低。
