Accéder directement au contenu Accéder directement à la navigation
Nouvelle interface
Article dans une revue

Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

Geffen Kleinstern Nicola Camp Lynn R. Goldin 1 Celine Vachon Claire Vajdic Silvia de Sanjosé 2 J. Brice Weinberg Yolanda Benavente 3 Delphine Casabonne Mark Liebow Alexandra Nieters 4 Henrik Hjalgrim Mads Melbye 5 Bengt Glimelius 6 Hans-Olov Adami 7 Paolo Boffetta 8 Paul Brennan 9 Marc Maynadié 10, 11, 12 James Mckay 13 Pier Luigi Cocco Tait Shanafelt 14 Timothy Call Aaron Norman 15 Curtis Hanson Dennis Robinson Kari Chaffee Angela Brooks-Wilson Alain A. Monnereau 16, 17, 18 Jacqueline Clavel 17, 18 Martha Glenn 19 Karen Curtin 19 Lucia Conde Paige Bracci Lindsay M. Morton 1 Wendy Cozen 20 Richard K. Severson 21 Stephen Chanock 22 John Spinelli James Johnston Nathaniel Rothman 1 Christine Skibola 23 Jose Leis Neil Kay Karin Smedby 24 Sonja I Berndt 1 James Cerhan 14 Neil Caporaso 1 Susan L. Slager 25, 14 
Abstract : Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.
Type de document :
Article dans une revue
Liste complète des métadonnées
Contributeur : LNC - université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mercredi 13 mars 2019 - 11:58:12
Dernière modification le : dimanche 26 juin 2022 - 01:55:26

Lien texte intégral



Geffen Kleinstern, Nicola Camp, Lynn R. Goldin, Celine Vachon, Claire Vajdic, et al.. Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood, 2018, 131 (23), pp.2541-2551. ⟨10.1182/blood-2017-11-814608⟩. ⟨hal-02066279⟩



Consultations de la notice