Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

• DOI: 10.3389/fonc.2021.771312
• Publication Date: 2021-12-03T05:41:05Z
• Authors: Ye Lu; Manuel Gentiluomo; Angelica Macauda; Domenica Gioffreda; Maria Gazouli; Maria C. Petrone; Dezső Kelemen; Laura Ginocchi; Luca Morelli; Konstantinos Papiris; William Greenhalf; Jakob R. Izbicki; Vytautas Kiudelis; Beatrice Mohelník...; Bas Bueno-de-Mesq...; Pavel Vodicka; Hermann Brenner; Markus K. Diener; Raffaele Pezzilli; Audrius Ivanauskas; Roberto Salvia; Andrea Szentesi; Mateus Nóbrega Aoki; Balázs C. Németh; Cosimo Sperti; Krzysztof Jamroziak; Roger Chammas; Martin Oliverius; Livia Archibugi; Stefano Ermini; János Novák; Juozas Kupcinskas; Ondřej Strouhal; Pavel Souček; Giulia M. Cavestro; Anna C. Milanetto; Giuseppe Vanella; John P. Neoptolemos; George E. Theodor...; Hanneke W. M. van...; Andrea Mambrini; Stefania Moz; Zdenek Kala; Martin Loveček; Daniela Basso; Faik G. Uzunoglu; Thilo Hackert; Sabrina G. G. Tes...; Viktor Hlaváč; Angelo Andriulli; Maurizio Lucchesi; Francesca Tavano; Silvia Carrara; Péter Hegyi; Paolo G. Arcidiacono; Olivier R. Busch; Rita T. Lawlor; Marta Puzzono; Ugo Boggi; Feng Guo; Ewa Małecka-Panas; Gabriele Capurso; Stefano Landi; Renata Talar-Wojn...; Oliver Strobel; Xin Gao; Yogesh Vashist; Daniele Campa; Federico Canzian
• Keywords: Genome-wide Association Study; Genetic Association; genetic model

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much the heritability risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional variants. To discover recessively inherited loci, we performed re-analysis largest GWAS, Pancreatic Cancer Cohort Consortium (PanScan) and Case-Control (PanC4), including 8,769 cases 7,055 controls ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with according to inheritance. We replicated these variants 3,212 3,470 collected from PANcreatic Disease ReseArch (PANDoRA) consortium. The results meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) rs147904962 (17q21.31) specific effects (p<10 −5 ) compared additive (p>10 −3 ), although none six SNPs reached conventional threshold significance (p < 5×10 −8 ). Additional bioinformatic analysis explored functional annotations indicated possible relationship between rs36018702 expression BCL2L11 BUB1 genes, which are known involved biology. Our findings, while not conclusive, indicate importance considering non-additive models when performing GWAS analysis. associated this study used further meta-analysis might useful addiction improve performance polygenic scores.