Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Result description
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 x 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 x 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.
Keywords
marginal zone lymphomadiffuse large B-cell lymphomafollicular lymphomachronic lymphocytic leukemiahomozygosityNon-Hodgkin lymphoma
The result's identifiers
Result code in IS VaVaI
Result on the web
DOI - Digital Object Identifier
Alternative languages
Result language
angličtina
Original language name
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Original language description
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 x 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 x 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.
Czech name
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Czech description
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Classification
Type
Jost - Miscellaneous article in a specialist periodical
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of translational genetics and genomics
ISSN
2578-5281
e-ISSN
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Volume of the periodical
5
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
200-217
UT code for WoS article
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EID of the result in the Scopus database
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Basic information
Result type
Jost - Miscellaneous article in a specialist periodical
OECD FORD
Oncology
Year of implementation
2021