Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Berndt, S. I. et al. (2022) Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes. Leukemia, 36(12), pp. 2835-2844. (doi: 10.1038/s41375-022-01711-0) (PMID:36273105)

[img] Text
284820.pdf - Accepted Version

[img] Image
284820Suppl1.pdf - Supplemental Material



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 ) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10 ). 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 ), 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. [Abstract copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.]

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lake, Ms Annette and Jarrett, Professor Ruth
Authors: 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., 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., and Rothman, N.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Leukemia
Publisher:Springer Nature
ISSN (Online):1476-5551
Published Online:22 October 2022
Copyright Holders:Copyright © 2022 This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply
First Published:First published in Leukemia 36(12): 2835-2844
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record