探索尼安德特人对欧亚人胰导管腺癌风险的影响。
Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.
发表日期：2023 Aug 13
作者：
Margherita Piccardi, Manuel Gentiluomo, Stefania Bertoncini, Raffaele Pezzilli, Bálint Erőss, Stefania Bunduc, Faik G Uzunoglu, Renata Talar-Wojnarowska, Tomas Vanagas, Cosimo Sperti, Martin Oliverius, Mateus Nóbrega Aoki, Stefano Ermini, Tamás Hussein, Ugo Boggi, Krzysztof Jamroziak, Evaristo Maiello, Luca Morelli, Ludmila Vodickova, Gregorio Di Franco, Stefano Landi, Andrea Szentesi, Martin Lovecek, Marta Puzzono, Francesca Tavano, Hanneke W M van Laarhoven, Alessandro Zerbi, Beatrice Mohelnikova-Duchonova, Hannah Stocker, Eithne Costello, Gabriele Capurso, Laura Ginocchi, Rita T Lawlor, Giuseppe Vanella, Francesca Bazzocchi, Jakob R Izbicki, Anna Latiano, Bas Bueno-de-Mesquita, Ruggero Ponz de Leon Pisani, Ben Schöttker, Pavel Soucek, Péter Hegyi, Maria Gazouli, Thilo Hackert, Juozas Kupcinskas, Lina Poskiene, Matteo Tacelli, Susanne Roth, Silvia Carrara, Francesco Perri, Viktor Hlavac, George E Theodoropoulos, Olivier R Busch, Andrea Mambrini, Casper H J van Eijck, Paolo Arcidiacono, Aldo Scarpa, Claudio Pasquali, Daniela Basso, Maurizio Lucchesi, Anna Caterina Milanetto, John P Neoptolemos, Giulia Martina Cavestro, Dainius Janciauskas, Xuechen Chen, Roger Chammas, Mara Goetz, Hermann Brenner, Livia Archibugi, Michael Dannemann, Federico Canzian, Sergio Tofanelli, Daniele Campa
来源：
Experimental Hematology & Oncology
摘要：
现今的非洲以外地区人类基因组中，含有1-3%源自尼安德特人的DNA，这是50-60万年前尼安德特人与解剖学上现代人发生混合事件的后果。与胰管腺癌（PDAC）相关的尼安德特人导入的单核苷酸多态性（aSNPs），与现代人的疾病相关特征有关，如肥胖、2型糖尿病和炎症。在本研究中，我们旨在调查三个欧亚种群中aSNPs在PDAC中的作用。使用高覆盖的Vindija尼安德特人基因组，从1000人基因组计划第3阶段数据中选择非非洲族群的aSNPs。然后，利用超过200,000个个体的已有GWAS数据，在欧洲人和东亚人中独立测试aSNPs与PDAC风险之间的关联。我们在欧洲血统样本中没有发现aSNPs与PDAC之间的显著相关性，而在东亚人群中，我们观察到Chr10p12.1-rs117585753-T等位基因（MAF = 10%）增加了PDAC发病的风险（OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10-6），其P值接近考虑多次检验的阈值。我们的结果显示，尼安德特SNPs对于PDAC风险只有很小的贡献。© 2023. 智利生物学协会。
The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations.The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10-6), with a P-value close to a threshold that takes into account multiple testing.Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.© 2023. Sociedad de Biologia de Chile.