Journal Article

DKFZ-2022-02510

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.

Berndt, S. I. ; Vijai, J. ; Benavente, Y. ; Camp, N. J. ; Nieters, A. ; Wang, Z. ; Smedby, K. E. ; Kleinstern, G. ; Hjalgrim, H. ; Besson, C. ; Skibola, C. F. ; Morton, L. M. ; Brooks-Wilson, A. R. ; Teras, L. R. ; Breeze, C. ; Arias, J. ; Adami, H.-O. ; Albanes, D. ; Anderson, K. C. ; Ansell, S. M. ; Bassig, B. ; Becker, N.DKFZ* ; Bhatti, P. ; Birmann, B. M. ; Boffetta, P. ; Bracci, P. M. ; Brennan, P. ; Brown, E. E. ; Burdett, L. ; Cannon-Albright, L. A. ; Chang, E. T. ; Chiu, B. C. H. ; Chung, C. C. ; Clavel, J. ; Cocco, P. ; Colditz, G. ; Conde, L. ; Conti, D. V. ; Cox, D. G. ; Curtin, K. ; Casabonne, D. ; De Vivo, I. ; Diver, W. R. ; Dogan, A. ; Edlund, C. K. ; Foretova, L. ; Fraumeni, J. F. ; Gabbas, A. ; Ghesquières, H. ; Giles, G. G. ; Glaser, S. ; Glenn, M. ; Glimelius, B. ; Gu, J. ; Habermann, T. M. ; Haiman, C. A. ; Haioun, C. ; Hofmann, J. N. ; Holford, T. R. ; Holly, E. A. ; Hutchinson, A. ; Izhar, A. ; Jackson, R. D. ; Jarrett, R. F. ; Kaaks, R. ; Kane, E. ; Kolonel, L. N. ; Kong, Y. ; Kraft, P. ; Kricker, A. ; Lake, A. ; Lan, Q. ; Lawrence, C. ; Li, D. ; Liebow, M. ; Link, B. K. ; Magnani, C. ; Maynadie, M. ; McKay, J. ; Melbye, M. ; Miligi, L. ; Milne, R. L. ; Molina, T. J. ; Monnereau, A. ; Montalvan, R. ; North, K. E. ; Novak, A. J. ; Onel, K. ; Purdue, M. P. ; Rand, K. A. ; Riboli, E. ; Riby, J. ; Roman, E. ; Salles, G. ; Sborov, D. W. ; Severson, R. K. ; Shanafelt, T. D. ; Smith, M. T. ; Smith, A. ; Song, K. W. ; Song, L. ; Southey, M. C. ; Spinelli, J. J. ; Staines, A. ; Stephens, D. ; Sutherland, H. J. ; Tkachuk, K. ; Thompson, C. A. ; Tilly, H. ; Tinker, L. F. ; Travis, R. C. ; Turner, J. ; Vachon, C. M. ; Vajdic, C. M. ; Van Den Berg, A. ; Van Den Berg, D. J. ; Vermeulen, R. C. H. ; Vineis, P. ; Wang, S. S. ; Weiderpass, E. ; Weiner, G. J. ; Weinstein, S. ; Doo, N. W. ; Ye, Y. ; Yeager, M. ; Yu, K. ; Zeleniuch-Jacquotte, A. ; Zhang, Y. ; Zheng, T. ; Ziv, E. ; Sampson, J. ; Chatterjee, N. ; Offit, K. ; Cozen, W. ; Wu, X. ; Cerhan, J. R. ; Chanock, S. J. ; Slager, S. L. ; Rothman, N.

2022
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41375-022-01711-0

Abstract: 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.

Note: 2022 Dec;36(12):2835-2844

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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