Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes Journal Article

   


Authors: Moore, A.; Machiela, M. J.; Machado, M.; Wang, S. S.; Kane, E.; Slager, S. L.; Zhou, W.; Carrington, M.; Lan, Q.; Milne, R. L.; Birmann, B. M.; Adami, H. O.; Albanes, D.; Arslan, A. A.; Becker, N.; Benavente, Y.; Bisanzi, S.; Boffetta, P.; Bracci, P. M.; Brennan, P.; Brooks-Wilson, A. R.; Canzian, F.; Caporaso, N.; Clavel, J.; Cocco, P.; Conde, L.; Cox, D. G.; Cozen, W.; Curtin, K.; De Vivo, I.; de Sanjose, S.; Foretova, L.; Gapstur, S. M.; Ghesquières, H.; Giles, G. G.; Glenn, M.; Glimelius, B.; Gao, C.; Habermann, T. M.; Hjalgrim, H.; Jackson, R. D.; Liebow, M.; Link, B. K.; Maynadie, M.; McKay, J.; Melbye, M.; Miligi, L.; Molina, T. J.; Monnereau, A.; Nieters, A.; North, K. E.; Offit, K.; Patel, A. V.; Piro, S.; Ravichandran, V.; Riboli, E.; Salles, G.; Severson, R. K.; Skibola, C. F.; Smedby, K. E.; Southey, M. C.; Spinelli, J. J.; Staines, A.; Stewart, C.; Teras, L. R.; Tinker, L. F.; Travis, R. C.; Vajdic, C. M.; Vermeulen, R. C. H.; Vijai, J.; Weiderpass, E.; Weinstein, S.; Doo, N. W.; Zhang, Y.; Zheng, T.; Chanock, S. J.; Rothman, N.; Cerhan, J. R.; Dean, M.; Camp, N. J.; Yeager, M.; Berndt, S. I.
Article Title: Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Abstract: Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (β = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk. © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: homozygosity; follicular lymphoma; marginal zone lymphoma; diffuse large b-cell lymphoma; non-hodgkin lymphoma; chronic lymphocytic leukemia
Journal Title: Journal of Translational Genetics and Genomics
Volume: 5
Issue: 2
ISSN: 2578-5281
Publisher: OAE Publishing Inc.  
Date Published: 2021-01-01
Start Page: 200
End Page: 217
Language: English
DOI: 10.20517/jtgg.2021.08
PROVIDER: scopus
PMCID: PMC8494431
PUBMED: 34622145
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85153859752&doi=10.20517%2fjtgg.2021.08&partnerID=40&md5=599e974d222449d7db3a860fe316d4ab
Notes: Article -- Export Date: 1 June 2023 -- Source: Scopus
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  1. Kenneth Offit
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  2. Vijai Joseph
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  3. Vignesh Ravichandran
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  4. Carolyn R Stewart
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