RT Journal Article
T1 Validation and functional characterization of GWAS-identified variants for chronic lymphocytic leukemia: a CRuCIAL study.
A1 Garcia-Martin, Paloma
A1 Diez, Ana Moñiz
A1 Maldonado, Jose Manuel Sanchez
A1 Serrano, Antonio Jose Cabrera
A1 Ter Horst, Rob
A1 Benavente, Yolanda
A1 Landi, Stefano
A1 Macauda, Angelica
A1 Clay-Gilmour, Alyssa
A1 Hernandez-Mohedo, Francisca
A1 Niazi, Yasmeen
A1 Gonzalez-Sierra, Pedro
A1 Espinet, Blanca
A1 Rodriguez-Sevilla, Juan Jose
A1 Maffei, Rossana
A1 Blanco, Gonzalo
A1 Giaccherini, Matteo
A1 Puiggros, Anna
A1 Cerhan, James
A1 Marasca, Roberto
A1 Cañadas-Garre, Marisa
A1 Lopez-Nevot, Miguel Angel
A1 Chen-Liang, Tzu
A1 Thomsen, Hauke
A1 Gamez, Irene
A1 Moreno, Víctor
A1 Marcos-Gragera, Rafael
A1 Garcia-Alvarez, Maria
A1 Llorca, Javier
A1 Jerez, Andres
A1 Berndt, Sonja
A1 Butrym, Aleksandra
A1 Norman, Aaron D
A1 Casabonne, Delphine
A1 Luppi, Mario
A1 Slager, Susan L
A1 Hemminki, Kari
A1 Li, Yang
A1 Alcoceba, Miguel
A1 Campa, Daniele
A1 Canzian, Federico
A1 de Sanjose, Silvia
A1 Försti, Asta
A1 Netea, Mihai G
A1 Jurado, Manuel
A1 Sainz, Juan
K1 Genetic Predisposition to Disease
K1 Genome-Wide Association Study
K1 Humans
K1 Leukemia, Lymphocytic, Chronic, B-Cell
K1 Polymorphism, Single Nucleotide
AB During the past years, considerable efforts have been made to uncover the genetic component of chronic lymphocytic leukemia (CLL) susceptibility. To date, several genome-wide association studies (GWAS) and their meta- analysis have identified not only single-nucleotide polymorphisms (SNPs) associated with CLL risk [1] but also patient survival [2]. However, despite these noticeable results, it becomes evident that both validation and functional characterization of the genetic variations identified are still required before they can be used in a clinical setting. Hence, we decided to validate the association of 41 GWAS-identified hits for CLL in 1158 CLL cases and 1947 controls ascertained through the Consortium for Research in Chronic lymphocytIc Leukemia (CRuCIAL) and to investigate their impact on modulating host immune responses and their utility to predict disease onset. Study participants were of European ancestry and gave their written informed consent to participate in the study, which was approved by the ethical review committee of participant institutions. CLL patients had often Binet stage A and Rai stage I (67.00% and 79.83%) and, compared to controls, had a higher mean age (66.19 ± 12.66 vs. 55.60 ± 11.50) and an increased male/female ratio (1.54 vs. 0.91). SNPs selection was based on published GWAS, functionality according to HaploReg data, and linkage disequilibrium between the SNPs. Genotyping of genetic variants was performed using KASPTM and Taqman® assays. Hardy–Weinberg equilibrium was assessed in the controls (P > 0.001) and the association between CLL and SNPs was tested using a multivariate unconditional  logistic regression analysis adjusted for age, sex, and country of origin. A meta-analysis of the CRuCIAL results with those from previous GWAS was conducted to validate genetic associations and the I [2] statistic was used to assess statistical heterogeneity between the studies (PHet > 0.01).
PB Nature Publishing Group
YR 2022
FD 2022-05-04
LK http://hdl.handle.net/10668/19517
UL http://hdl.handle.net/10668/19517
LA en
NO García-Martín P, Díez AM, Maldonado JMS, Serrano AJC, Ter Horst R, Benavente Y, et al. Validation and functional characterization of GWAS-identified variants for chronic lymphocytic leukemia: a CRuCIAL study. Blood Cancer J. 2022 May 17;12(5):79.
DS RISalud
RD Apr 11, 2025