Journal article
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Journal of translational genetics and genomics, Vol.5, pp.200-217
2021
DOI: 10.20517/jtgg.2021.08
PMCID: PMC8494431
PMID: 34622145
Abstract
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.
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.
We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41,
= 1.6 × 10
) and FL (β = 11.4, SE = 5.82,
= 0.02) but not DLBCL (
= 1.0) or MZL (
= 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51,
= 2.4 × 10
). 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.
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.
Details
- Title: Subtitle
- Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
- Creators
- Amy Moore - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAMitchell J Machiela - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAMoara Machado - Universidade Federal de Minas GeraisSophia S Wang - City Of Hope National Medical CenterEleanor Kane - University of YorkSusan L Slager - Mayo ClinicWeiyin Zhou - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD 20877, USAMary Carrington - Ragon Institute of MGH, MIT and HarvardQing Lan - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USARoger L Milne - Monash UniversityBrenda M Birmann - Brigham and Women's HospitalHans-Olov Adami - Karolinska InstitutetDemetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAAlan A Arslan - New York UniversityNikolaus Becker - German Cancer Research CenterYolanda Benavente - Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Barcelona 08036, SpainSimonetta Bisanzi - Florence (Netherlands)Paolo Boffetta - University of BolognaPaige M Bracci - University of California, San FranciscoPaul Brennan - Centre international de recherche sur le cancerAngela R Brooks-Wilson - Simon Fraser UniversityFederico Canzian - German Cancer Research CenterNeil Caporaso - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAJacqueline Clavel - Sorbonne Paris CitéPierluigi Cocco - University of CagliariLucia Conde - University College LondonDavid G Cox - InsermWendy Cozen - University of Southern CaliforniaKaren Curtin - University of UtahImmaculata De Vivo - Harvard UniversitySilvia de Sanjose - Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Barcelona 08036, SpainLenka Foretova - Masaryk Memorial Cancer InstituteSusan M Gapstur - American Cancer SocietyHervè Ghesquières - InsermGraham G Giles - Monash UniversityMartha Glenn - University of UtahBengt Glimelius - Uppsala UniversityChi Gao - Harvard UniversityThomas M Habermann - Mayo ClinicHenrik Hjalgrim - Statens Serum InstitutRebecca D Jackson - The Ohio State UniversityMark Liebow - Mayo Clinic in FloridaBrian K Link - University of IowaMarc Maynadie - Université de BourgogneJames McKay - Centre international de recherche sur le cancerMads Melbye - Stanford UniversityLucia Miligi - Florence (Netherlands)Thierry J Molina - Délégation Paris 5Alain Monnereau - Institut BergoniéAlexandra Nieters - University Medical Center FreiburgKari E North - University of North Carolina at Chapel HillKenneth Offit - Memorial Sloan Kettering Cancer CenterAlpa V Patel - American Cancer SocietySara Piro - Florence (Netherlands)Vignesh Ravichandran - Memorial Sloan Kettering Cancer CenterElio Riboli - Imperial College LondonGilles Salles - InsermRichard K Severson - Wayne State UniversityChristine F Skibola - Emory UniversityKarin E Smedby - Karolinska InstitutetMelissa C Southey - The University of MelbourneJohn J Spinelli - University of British ColumbiaAnthony Staines - Dublin City UniversityCarolyn Stewart - Memorial Sloan Kettering Cancer CenterLauren R Teras - American Cancer SocietyLesley F Tinker - Fred Hutch Cancer CenterRuth C Travis - University of OxfordClaire M Vajdic - UNSW SydneyRoel C H Vermeulen - University Medical Center UtrechtJoseph Vijai - Memorial Sloan Kettering Cancer CenterElisabete Weiderpass - Centre international de recherche sur le cancerStephanie Weinstein - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USANicole Wong Doo - The University of SydneyYawei Zhang - Yale UniversityTongzhang Zheng - Brown UniversityStephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USANathaniel Rothman - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USAJames R Cerhan - Mayo Clinic in FloridaMichael Dean - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USANicola J Camp - University of UtahMeredith Yeager - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD 20877, USASonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
- Resource Type
- Journal article
- Publication Details
- Journal of translational genetics and genomics, Vol.5, pp.200-217
- DOI
- 10.20517/jtgg.2021.08
- PMID
- 34622145
- PMCID
- PMC8494431
- NLM abbreviation
- J Transl Genet Genom
- ISSN
- 2578-5281
- eISSN
- 2578-5281
- Grant note
- R01 CA092153 / NCI NIH HHS U58 DP000807 / NCCDPHP CDC HHS R01 CA154643 / NCI NIH HHS HHSN268201100004I / NHLBI NIH HHS R01 CA200703 / NCI NIH HHS R01 CA062006 / NCI NIH HHS U01 CA049449 / NCI NIH HHS HHSN268201100004C / WHI NIH HHS R01 CA098122 / NCI NIH HHS HHSN268201100002C / WHI NIH HHS HHSN261201000035C / NCI NIH HHS N01CO12400 / NCI NIH HHS HHSN268201100003C / WHI NIH HHS R01 CA134958 / NCI NIH HHS P30 ES000260 / NIEHS NIH HHS UL1 TR000135 / NCATS NIH HHS P01 CA087969 / NCI NIH HHS K08 CA134919 / NCI NIH HHS HHSN268201100046C / NHLBI NIH HHS R01 CA134674 / NCI NIH HHS P30 CA042014 / NCI NIH HHS HHSN261201000035I / NCI NIH HHS HHSN271201100004C / NIA NIH HHS U01 HG007033 / NHGRI NIH HHS N01 PC067008 / NCI NIH HHS N01 PC065064 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS HHSN268201100003I / NHLBI NIH HHS HHSN261201000140C / NCI NIH HHS R01 CA148690 / NCI NIH HHS U01 CA167552 / NCI NIH HHS R01 CA098661 / NCI NIH HHS HHSN268201100002I / NHLBI NIH HHS N01 PC067010 / NCI NIH HHS HHSN268201100001C / WHI NIH HHS HHSN261200800001C / CCR NIH HHS HHSN261201000034C / NCI NIH HHS ZIA CP010136 / Intramural NIH HHS P30 CA086862 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS R01 CA149445 / NCI NIH HHS HHSN268201100001I / NHLBI NIH HHS R01 CA049449 / NCI NIH HHS U01 CA118444 / NCI NIH HHS R21 CA165923 / NCI NIH HHS HHSN261201000026C / NCI NIH HHS P30 CA016087 / NCI NIH HHS N01 PC067009 / NCI NIH HHS HHSN261200800001E / NCI NIH HHS
- Language
- English
- Date published
- 2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984362667302771
Metrics
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