Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
2022
Berndt, Sonja I. | Vijai, Joseph | Benavente, Yolanda | Camp, Nicola J | Nieters, Alexandra | Wang, Zhaoming | Smedby, Karin E. | Kleinstern, Geffen | Hjalgrim, Henrik | Besson, Caroline | Skibola, Christine F. | Morton, Lindsay M. | Brooks-Wilson, Angela R. | Teras, Lauren R. | Breeze, Charles | Arias, Joshua | Adami, Hans-Olov | Albanes, Demetrius | Anderson, Kenneth C. | Ansell, Stephen M. | Bassig, Bryan | Becker, Nikolaus | Bhatti, Parveen | Birmann, Brenda M. | Boffetta, Paolo | Bracci, Paige M | Brennan, Paul | Brown, Elizabeth E. | Burdett, Laurie | Cannon-Albright, Lisa A. | Chang, Ellen T. | Chiu, Brian C. H. | Chung, Charles C. | Clavel, Jacqueline | Cocco, Pierluigi | Colditz, Graham | Conde, Lucia | Conti, David V. | Cox, David G. | Curtin, Karen | Casabonne, Delphine | de Vivo, Immaculata | Diver, W. Ryan | Dogan, Ahmet | Edlund, Christopher K. | Foretova, Lenka | Fraumeni, Joseph F. Jr | Gabbas, Attilio | Ghesquieres, Herve | Giles, Graham G. | Glaser, Sally | Glenn, Martha | Glimelius, Bengt | Gu, Jian | Habermann, Thomas M. | Haiman, Christopher A. | Haioun, Corinne | Hofmann, Jonathan N. | Holford, Theodore R. | Holly, Elizabeth A. | Hutchinson, Amy | Izhar, Aalin | Jackson, Rebecca D. | Jarrett, Ruth F. | Kaaks, Rudolph | Kane, Eleanor | Kolonel, Laurence N. | Kong, Yinfei | Kraft, Peter | Kricker, Anne | Lake, Annette | Lan, Qing | Lawrence, Charles | Li, Dalin | Liebow, Mark | Link, Brian K. | Magnani, Corrado | Maynadie, Marc | Mckay, James | Melbye, Mads | Miligi, Lucia | Milne, Roger L. | Molina, Thierry J. | Monnereau, Alain | Montalvan, Rebecca | North, Kari E. | Novak, Anne J. | Onel, Kenan | Purdue, Mark P. | Rand, Kristin A. | Riboli, Elio | Riby, Jacques | Roman, Eve | Salles, Gilles | Sborov, Douglas W. | Severson, Richard K. | Shanafelt, Tait D. | Smith, Martyn T. | Smith, Alexandra | Song, Kevin W. | Song, Lei | Southey, Melissa C. | Spinelli, John J. | Staines, Anthony | Stephens, Deborah | Sutherland, Heather J. | Tkachuk, Kaitlyn | Thompson, Carrie A. | Tilly, Herve | Tinker, Lesley F. | Travis, Ruth C. | Turner, Jenny | Vachon, Celine M. | Vajdic, Claire M. | van den Berg, Anke | van den Berg, David J. | Vermeulen, Roel C. H. | Vineis, Paolo | Wang, Sophia S. | Weiderpass, Elisabete | Weiner, George J. | Weinstein, Stephanie | Doo, Nicole Wong | Ye, Yuanqing | Yeager, Meredith | Yu, Kai | Zeleniuch-Jacquotte, Anne | Zhang, Yawei | Zheng, Tongzhang | Ziv, Elad | Sampson, Joshua | Chatterjee, Nilanjan | Offit, Kenneth | Cozen, Wendy | Wu, Xifeng | Cerhan, James R. | Chanock, Stephen J. | Slager, Susan L. | Rothman, Nathaniel | Centre de recherche en épidémiologie et santé des populations (CESP) ; Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay | Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques (CRESS (U1153 / UMR_A 1125)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Immuno-Biologie des Lymphomes [CIRI] (CIRI-LIB) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL] ; Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) ; Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL) | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) | Bordeaux population health (BPH) ; Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
International audience
Mostrar más [+] Menos [-]Inglés. Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10(-8)) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10(-9)). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10(-8)), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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