RT Journal Article
T1 A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.
A1 Lopez de Maturana, Evangelina
A1 Rodriguez, Juan Antonio
A1 Alonso, Lola
A1 Lao, Oscar
A1 Molina-Montes, Esther
A1 Martin-Antoniano, Isabel Adoracion
A1 Gomez-Rubio, Paulina
A1 Lawlor, Rita
A1 Carrato, Alfredo
A1 Hidalgo, Manuel
A1 Iglesias, Mar
A1 Molero, Xavier
A1 Löhr, Matthias
A1 Michalski, Christopher
A1 Perea, Jose
A1 O'Rorke, Michael
A1 Barbera, Victor Manuel
A1 Tardon, Adonina
A1 Farre, Antoni
A1 Muñoz-Bellvis, Luis
A1 Crnogorac-Jurcevic, Tanja
A1 Dominguez-Muñoz, Enrique
A1 Gress, Thomas
A1 Greenhalf, William
A1 Sharp, Linda
A1 Arnes, Luis
A1 Cecchini, Lluis
A1 Balsells, Joaquim
A1 Costello, Eithne
A1 Ilzarbe, Lucas
A1 Kleeff, Jörg
A1 Kong, Bo
A1 Márquez, Mirari
A1 Mora, Josefina
A1 O'Driscoll, Damian
A1 Scarpa, Aldo
A1 Ye, Weimin
A1 Yu, Jingru
A1 Garcia-Closas, Montserrat
A1 Kogevinas, Manolis
A1 Rothman, Nathaniel
A1 Silverman, Debra T
A1 Albanes, Demetrius
A1 Arslan, Alan A
A1 Beane-Freeman, Laura
A1 Bracci, Paige M
A1 Brennan, Paul
A1 Bueno-de-Mesquita, Bas
A1 Buring, Julie
A1 Canzian, Federico
A1 Du, Margaret
A1 Gallinger, Steve
A1 Gaziano, J Michael
A1 Goodman, Phyllis J
A1 Gunter, Marc
A1 LeMarchand, Loic
A1 Li, Donghui
A1 Neale, Rachael E
A1 Peters, Ulrika
A1 Petersen, Gloria M
A1 Risch, Harvey A
A1 Sanchez-Perez, Maria-Jose
A1 Shu, Xiao-Ou
A1 Thornquist, Mark D
A1 Visvanathan, Kala
A1 Zheng, Wei
A1 Chanock, Stephen J
A1 Easton, Douglas
A1 Wolpin, Brian M
A1 Stolzenberg-Solomon, Rachael Z
A1 Klein, Alison P
A1 Amundadottir, Laufey T
A1 Marti-Renom, Marc A
A1 Real, Francisco X
A1 Malats, Nuria
K1 3D genomic structure
K1 Genetic susceptibility
K1 Genome-wide association analysis
K1 Local indices of genome spatial autocorrelation
K1 Pancreatic cancer risk
AB Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support. This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.
PB BioMed Central Ltd.
YR 2020
FD 2020-12-03
LK http://hdl.handle.net/10668/17074
UL http://hdl.handle.net/10668/17074
LA en
NO López de Maturana E, Rodríguez JA, Alonso L, Lao O, Molina-Montes E, Martín-Antoniano IA,  et al. A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer. Genome Med. 2021 Feb 1;13(1):15.
DS RISalud
RD Apr 8, 2025