美国Lerner研究所Ignacio Mata等研究人员合作完成帕金森病的多基因组全关联荟萃分析。该研究于2023年12月28日在线发表于国际一流学术期刊《自然—遗传学》。

研究人员对49049例帕金森病病例、18785例代理病例和2458063例对照进行了大规模的多血统荟萃分析，其中包括欧洲、东亚、拉丁美洲和非洲血统的个体。在一项荟萃分析中，研究人员确定了78个独立的全基因组重要位点，包括12个潜在的新位点（MTF2、PIK3CA、ADD1、SYBU、IRS2、USP8、PIGL、FASN、MYLK2、USP25、EP300 和 PPP6R2），并在6个已知的帕金森病位点上精细绘制了6个推测的因果变异。

通过将这些研究结果与公开的eQTL数据相结合，研究人员在这些新基因位点上确定了25个推测风险基因，这些基因的表达与帕金森病风险有关。这项工作为今后在非欧洲人群中鉴定帕金森病基因位点的工作奠定了基础。

据介绍，虽然通过全基因组关联研究发现了90多种帕金森病的独立风险变异，但大多数研究都是在一个人群中进行的。

附：英文原文

Title: Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Author: Kim, Jonggeol Jeffrey, Vitale, Dan, Otani, Diego Vliz, Lian, Michelle Mulan, Heilbron, Karl, Iwaki, Hirotaka, Lake, Julie, Solsberg, Caroline Warly, Leonard, Hampton, Makarious, Mary B., Tan, Eng-King, Singleton, Andrew B., Bandres-Ciga, Sara, Noyce, Alastair J., Blauwendraat, Cornelis, Nalls, Mike A., Foo, Jia Nee, Mata, Ignacio

Issue&Volume: 2023-12-28

Abstract: Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

DOI: 10.1038/s41588-023-01584-8

Source: https://www.nature.com/articles/s41588-023-01584-8