Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes Journal Article
| 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. Jr.; 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. |
| Article Title: | Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes |
| 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. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
| Keywords: | controlled study; major clinical study; single nucleotide polymorphism; case control study; genetics; case-control studies; polymorphism, single nucleotide; genetic predisposition to disease; multiple myeloma; germ cell; gene locus; genome-wide association study; risk factors; risk factor; acute lymphoblastic leukemia; hodgkin disease; carcinogenesis; germ cells; nonhodgkin lymphoma; lymphoma, non-hodgkin; genetic susceptibility; cancer classification; chronic lymphatic leukemia; genetic predisposition; follicular lymphoma; marginal zone lymphoma; heritability; chromosome 10q; genetic correlation; genotyping; diffuse large b cell lymphoma; humans; human; article; genetic risk score |
| Journal Title: | Leukemia |
| Volume: | 36 |
| Issue: | 12 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-12-01 |
| Start Page: | 2835 |
| End Page: | 2844 |
| Language: | English |
| DOI: | 10.1038/s41375-022-01711-0 |
| PUBMED: | 36273105 |
| PROVIDER: | scopus |
| PMCID: | PMC10337695 |
| DOI/URL: | |
| Notes: | Article -- Erratum issued, see DOI: 10.1038/s41375-023-01978-x -- Export Date: 3 January 2023 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work