探讨欧亚人群中胰腺导管腺癌风险的尼安德特人遗传遗产。

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

机构信息

Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Department of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy.

出版信息

Biol Res. 2023 Aug 13;56(1):46. doi: 10.1186/s40659-023-00457-y.

DOI:10.1186/s40659-023-00457-y

PMID:37574541

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10424372/

Abstract

BACKGROUND

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.

RESULTS

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), with a P-value close to a threshold that takes into account multiple testing.

CONCLUSIONS

Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

摘要

背景

现今非非洲人的基因组中，有 1-3%的是尼安德特人基因，这是因为大约 5 万到 6 万年前尼安德特人和解剖学上的现代人类之间发生了混合事件。尼安德特人遗传的单核苷酸多态性（aSNPs）与现代人类疾病相关特征有关，这些特征是胰腺导管腺癌（PDAC）的风险因素，如肥胖、2 型糖尿病和炎症。在这项研究中，我们旨在调查三个欧亚人群中 aSNPs 在 PDAC 中的作用。

结果

使用高覆盖率的文尼察尼安德特人基因组，从 1000 基因组计划第三阶段的数据中选择非非洲人群中的 aSNPs。然后，利用现有的超过 20 万个体的 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。我们没有发现欧洲血统样本中的 aSNPs 与 PDAC 之间存在任何显著关联，而在东亚人中，我们观察到 Chr10p12.1-rs117585753-T 等位基因（MAF=10%）增加了患 PDAC 的风险（OR=1.35，95%CI 1.19-1.54，P=3.59×10），接近考虑多重检验的阈值。