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

Amy Moore; Mitchell J. Machiela; Moara Machado; Sophia S. Wang; Eleanor Kane; Susan L. Slager; Weiyin Zhou; Mary Carrington; Qing Lan; Roger L. Milne; Brenda M. Birmann; Hans Olov Adami; Demetrius Albanes; Alan A. Arslan; Nikolaus Becker; Yolanda Benavente; Simonetta Bisanzi; Paolo Boffetta; Paige M. Bracci; Paul Brennan; Angela R. Brooks-Wilson; Federico Canzian; Neil Caporaso; Jacqueline Clavel; Pierluigi Cocco; Lucia Conde; David G. Cox; Wendy Cozen; Karen Curtin; Immaculata De Vivo; Silvia de Sanjose; Lenka Foretova; Susan M. Gapstur; Hervé Ghesquières; Graham G. Giles; Martha Glenn; Bengt Glimelius; Chi Gao; Thomas M. Habermann; Henrik Hjalgrim; Rebecca D. Jackson; Mark Liebow; Brian K. Link; Marc Maynadie; James McKay; Mads Melbye; Lucia Miligi; Thierry J. Molina; Alain Monnereau; Alexandra Nieters; Kari E. North; Kenneth Offit; Alpa V. Patel; Sara Piro; Vignesh Ravichandran; Elio Riboli; Gilles Salles; Richard K. Severson; Christine F. Skibola; Karin E. Smedby; Melissa C. Southey; John J. Spinelli; Anthony Staines; Carolyn Stewart; Lauren R. Teras; Lesley F. Tinker; Ruth C. Travis; Claire M. Vajdic; Roel C.H. Vermeulen; Joseph Vijai; Elisabete Weiderpass; Stephanie Weinstein; Nicole Wong Doo; Yawei Zhang; Tongzhang Zheng; Stephen J. Chanock; Nathaniel Rothman; James R. Cerhan; Michael Dean; Nicola J. Camp; Meredith Yeager; Sonja I. Berndt

doi:10.20517/jtgg.2021.08

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

Amy Moore
, Mitchell J. Machiela
, Moara Machado
, Sophia S. Wang
, Eleanor Kane
, Susan L. Slager
, Weiyin Zhou
, Mary Carrington
, Qing Lan
, Roger L. Milne
, Brenda M. Birmann
, Hans Olov Adami
, Demetrius Albanes
, Alan A. Arslan
, Nikolaus Becker
, Yolanda Benavente
, Simonetta Bisanzi
, Paolo Boffetta
, Paige M. Bracci
, Paul Brennan

Angela R. Brooks-Wilson, Federico Canzian, Neil Caporaso, Jacqueline Clavel, Pierluigi Cocco, Lucia Conde, David G. Cox, Wendy Cozen, Karen Curtin, Immaculata De Vivo, Silvia de Sanjose, Lenka Foretova, Susan M. Gapstur, Hervé Ghesquières, Graham G. Giles, Martha Glenn, Bengt Glimelius, Chi Gao, Thomas M. Habermann, Henrik Hjalgrim, Rebecca D. Jackson, Mark Liebow, Brian K. Link, Marc Maynadie, James McKay, Mads Melbye, Lucia Miligi, Thierry J. Molina, Alain Monnereau, Alexandra Nieters, Kari E. North, Kenneth Offit, Alpa V. Patel, Sara Piro, Vignesh Ravichandran, Elio Riboli, Gilles Salles, Richard K. Severson, Christine F. Skibola, Karin E. Smedby, Melissa C. Southey, John J. Spinelli, Anthony Staines, Carolyn Stewart, Lauren R. Teras, Lesley F. Tinker, Ruth C. Travis, Claire M. Vajdic, Roel C.H. Vermeulen, Joseph Vijai, Elisabete Weiderpass, Stephanie Weinstein, Nicole Wong Doo, Yawei Zhang, Tongzhang Zheng, Stephen J. Chanock, Nathaniel Rothman, James R. Cerhan, Michael Dean, Nicola J. Camp, Meredith Yeager, Sonja I. Berndt

National Institutes of Health
Universidade Federal de Minas Gerais
City of Hope National Med Center
University of York
Mayo Clinic Rochester, MN
Ragon Institute
Cancer Council Victoria
University of Melbourne
Monash University
Harvard University
Karolinska Institutet
University of Oslo
New York University
German Cancer Research Center
Parc Taulí Hospital Universitari
CIBER Epidemiología y Salud Pública (CIBERESP)
Institute for the Study and Prevention of Cancer
University of California at San Francisco
International Agency for Research on Cancer
Provincial Health Services Authority
Simon Fraser University
Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
University of Cagliari
University College London
Centre Léon Bérard
University of Southern California
University of Utah
Masaryk Memorial Cancer Institute
American Cancer Society
CRCL
Uppsala University
Statens Serum Institut
Ohio State University
University of Iowa
Université de Bourgogne
Stanford University
Université Paris Cité
Centre Georges-François Leclerc
University of Freiburg
University of North Carolina at Chapel Hill
Memorial Sloan-Kettering Cancer Center
Imperial College London
Hospices civils de Lyon
Universite Claude Bernard Lyon 1
Wayne State University
Emory University
University of British Columbia
Dublin City University
Fred Hutchinson Cancer Research Center
University of Oxford
University of New South Wales
Utrecht University
The University of Sydney
Yale University
Brown University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	200-217
Number of pages	18
Journal	Journal of Translational Genetics and Genomics
Volume	5
Issue number	2
DOIs	https://doi.org/10.20517/jtgg.2021.08
State	Published - 2021

Keywords

Non-Hodgkin lymphoma
chronic lymphocytic leukemia
diffuse large B-cell lymphoma
follicular lymphoma
homozygosity
marginal zone lymphoma

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10.20517/jtgg.2021.08

Cite this

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., ... Berndt, S. I. (2021). Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes. Journal of Translational Genetics and Genomics, 5(2), 200-217. https://doi.org/10.20517/jtgg.2021.08

@article{39333f34ba84443ab47b1ca4f85603bf,

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.",

keywords = "Non-Hodgkin lymphoma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, homozygosity, marginal zone lymphoma",

author = "Amy Moore and Machiela, \{Mitchell J.\} and Moara Machado and Wang, \{Sophia S.\} and Eleanor Kane and Slager, \{Susan L.\} and Weiyin Zhou and Mary Carrington and Qing Lan and Milne, \{Roger L.\} and Birmann, \{Brenda M.\} and Adami, \{Hans Olov\} and Demetrius Albanes and Arslan, \{Alan A.\} and Nikolaus Becker and Yolanda Benavente and Simonetta Bisanzi and Paolo Boffetta and Bracci, \{Paige M.\} and Paul Brennan and Brooks-Wilson, \{Angela R.\} and Federico Canzian and Neil Caporaso and Jacqueline Clavel and Pierluigi Cocco and Lucia Conde and Cox, \{David G.\} and Wendy Cozen and Karen Curtin and \{De Vivo\}, Immaculata and \{de Sanjose\}, Silvia and Lenka Foretova and Gapstur, \{Susan M.\} and Herv{\'e} Ghesqui{\`e}res and Giles, \{Graham G.\} and Martha Glenn and Bengt Glimelius and Chi Gao and Habermann, \{Thomas M.\} and Henrik Hjalgrim and Jackson, \{Rebecca D.\} and Mark Liebow and Link, \{Brian K.\} and Marc Maynadie and James McKay and Mads Melbye and Lucia Miligi and Molina, \{Thierry J.\} and Alain Monnereau and Alexandra Nieters and North, \{Kari E.\} and Kenneth Offit and Patel, \{Alpa V.\} and Sara Piro and Vignesh Ravichandran and Elio Riboli and Gilles Salles and Severson, \{Richard K.\} and Skibola, \{Christine F.\} and Smedby, \{Karin E.\} and Southey, \{Melissa C.\} and Spinelli, \{John J.\} and Anthony Staines and Carolyn Stewart and Teras, \{Lauren R.\} and Tinker, \{Lesley F.\} and Travis, \{Ruth C.\} and Vajdic, \{Claire M.\} and Vermeulen, \{Roel C.H.\} and Joseph Vijai and Elisabete Weiderpass and Stephanie Weinstein and Doo, \{Nicole Wong\} and Yawei Zhang and Tongzhang Zheng and Chanock, \{Stephen J.\} and Nathaniel Rothman and Cerhan, \{James R.\} and Michael Dean and Camp, \{Nicola J.\} and Meredith Yeager and Berndt, \{Sonja I.\}",

note = "Publisher Copyright: {\textcopyright} 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.",

year = "2021",

doi = "10.20517/jtgg.2021.08",

language = "English",

volume = "5",

pages = "200--217",

journal = "Journal of Translational Genetics and Genomics",

issn = "2578-5281",

number = "2",

}

Moore, A, Machiela, MJ, Machado, M, Wang, SS, Kane, E, Slager, SL, Zhou, W, Carrington, M, Lan, Q, Milne, RL, Birmann, BM, Adami, HO, Albanes, D, Arslan, AA, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Bracci, PM, Brennan, P, Brooks-Wilson, AR, Canzian, F, Caporaso, N, Clavel, J, Cocco, P, Conde, L, Cox, DG, Cozen, W, Curtin, K, De Vivo, I, de Sanjose, S, Foretova, L, Gapstur, SM, Ghesquières, H, Giles, GG, Glenn, M, Glimelius, B, Gao, C, Habermann, TM, Hjalgrim, H, Jackson, RD, Liebow, M, Link, BK, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Molina, TJ, Monnereau, A, Nieters, A, North, KE, Offit, K, Patel, AV, Piro, S, Ravichandran, V, Riboli, E, Salles, G, Severson, RK, Skibola, CF, Smedby, KE, Southey, MC, Spinelli, JJ, Staines, A, Stewart, C, Teras, LR, Tinker, LF, Travis, RC, Vajdic, CM, Vermeulen, RCH, Vijai, J, Weiderpass, E, Weinstein, S, Doo, NW, Zhang, Y, Zheng, T, Chanock, SJ, Rothman, N, Cerhan, JR, Dean, M, Camp, NJ, Yeager, M & Berndt, SI 2021, 'Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes', Journal of Translational Genetics and Genomics, vol. 5, no. 2, pp. 200-217. https://doi.org/10.20517/jtgg.2021.08

TY - JOUR

T1 - Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes

AU - Moore, Amy

AU - Machiela, Mitchell J.

AU - Machado, Moara

AU - Wang, Sophia S.

AU - Kane, Eleanor

AU - Slager, Susan L.

AU - Zhou, Weiyin

AU - Carrington, Mary

AU - Lan, Qing

AU - Milne, Roger L.

AU - Birmann, Brenda M.

AU - Adami, Hans Olov

AU - Albanes, Demetrius

AU - Arslan, Alan A.

AU - Becker, Nikolaus

AU - Benavente, Yolanda

AU - Bisanzi, Simonetta

AU - Boffetta, Paolo

AU - Bracci, Paige M.

AU - Brennan, Paul

AU - Brooks-Wilson, Angela R.

AU - Canzian, Federico

AU - Caporaso, Neil

AU - Clavel, Jacqueline

AU - Cocco, Pierluigi

AU - Conde, Lucia

AU - Cox, David G.

AU - Cozen, Wendy

AU - Curtin, Karen

AU - De Vivo, Immaculata

AU - de Sanjose, Silvia

AU - Foretova, Lenka

AU - Gapstur, Susan M.

AU - Ghesquières, Hervé

AU - Giles, Graham G.

AU - Glenn, Martha

AU - Glimelius, Bengt

AU - Gao, Chi

AU - Habermann, Thomas M.

AU - Hjalgrim, Henrik

AU - Jackson, Rebecca D.

AU - Liebow, Mark

AU - Link, Brian K.

AU - Maynadie, Marc

AU - McKay, James

AU - Melbye, Mads

AU - Miligi, Lucia

AU - Molina, Thierry J.

AU - Monnereau, Alain

AU - Nieters, Alexandra

AU - North, Kari E.

AU - Offit, Kenneth

AU - Patel, Alpa V.

AU - Piro, Sara

AU - Ravichandran, Vignesh

AU - Riboli, Elio

AU - Salles, Gilles

AU - Severson, Richard K.

AU - Skibola, Christine F.

AU - Smedby, Karin E.

AU - Southey, Melissa C.

AU - Spinelli, John J.

AU - Staines, Anthony

AU - Stewart, Carolyn

AU - Teras, Lauren R.

AU - Tinker, Lesley F.

AU - Travis, Ruth C.

AU - Vajdic, Claire M.

AU - Vermeulen, Roel C.H.

AU - Vijai, Joseph

AU - Weiderpass, Elisabete

AU - Weinstein, Stephanie

AU - Doo, Nicole Wong

AU - Zhang, Yawei

AU - Zheng, Tongzhang

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Cerhan, James R.

AU - Dean, Michael

AU - Camp, Nicola J.

AU - Yeager, Meredith

AU - Berndt, Sonja I.

N1 - Publisher Copyright: © 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.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Non-Hodgkin lymphoma

KW - chronic lymphocytic leukemia

KW - diffuse large B-cell lymphoma

KW - follicular lymphoma

KW - homozygosity

KW - marginal zone lymphoma

UR - https://www.scopus.com/pages/publications/85153859752

U2 - 10.20517/jtgg.2021.08

DO - 10.20517/jtgg.2021.08

M3 - Article

AN - SCOPUS:85153859752

SN - 2578-5281

VL - 5

SP - 200

EP - 217

JO - Journal of Translational Genetics and Genomics

JF - Journal of Translational Genetics and Genomics

IS - 2

ER -

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

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Keywords

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