Author:
Piccardi Margherita,Gentiluomo Manuel,Bertoncini Stefania,Pezzilli Raffaele,Erőss Bálint,Bunduc Stefania,Uzunoglu Faik G.,Talar-Wojnarowska Renata,Vanagas Tomas,Sperti Cosimo,Oliverius Martin,Aoki Mateus Nóbrega,Ermini Stefano,Hussein Tamás,Boggi Ugo,Jamroziak Krzysztof,Maiello Evaristo,Morelli Luca,Vodickova Ludmila,Di Franco Gregorio,Landi Stefano,Szentesi Andrea,Lovecek Martin,Puzzono Marta,Tavano Francesca,van Laarhoven Hanneke W. M.,Zerbi Alessandro,Mohelnikova-Duchonova Beatrice,Stocker Hannah,Costello Eithne,Capurso Gabriele,Ginocchi Laura,Lawlor Rita T.,Vanella Giuseppe,Bazzocchi Francesca,Izbicki Jakob R.,Latiano Anna,Bueno-de-Mesquita Bas,Ponz de Leon Pisani Ruggero,Schöttker Ben,Soucek Pavel,Hegyi Péter,Gazouli Maria,Hackert Thilo,Kupcinskas Juozas,Poskiene Lina,Tacelli Matteo,Roth Susanne,Carrara Silvia,Perri Francesco,Hlavac Viktor,Theodoropoulos George E.,Busch Olivier R.,Mambrini Andrea,van Eijck Casper H. J.,Arcidiacono Paolo,Scarpa Aldo,Pasquali Claudio,Basso Daniela,Lucchesi Maurizio,Milanetto Anna Caterina,Neoptolemos John P.,Cavestro Giulia Martina,Janciauskas Dainius,Chen Xuechen,Chammas Roger,Goetz Mara,Brenner Hermann,Archibugi Livia,Dannemann Michael,Canzian Federico,Tofanelli Sergio,Campa Daniele
Abstract
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 × 10–6), 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.
Funder
Associazione Italiana Ricerca Cancro
Italian Ministry of Health
Ministry of Health of the Czech Republic
Cancer Research UK
Pancreatic Cancer UK Research Innovation Fund
Charles University Research Fund
Italian Ministry of Health grants to Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo (FG), Italy
“5x1000” voluntary contribution
Publisher
Springer Science and Business Media LLC