6533b827fe1ef96bd12866b3
RESEARCH PRODUCT
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Joseph VijaiHenrik HjalgrimRoger L. MilneRoger L. MilneRoger L. MilneSimonetta BisanziRebecca D. JacksonGraham G. GilesGraham G. GilesGraham G. GilesMark LiebowJohn J. SpinelliJohn J. SpinelliStephanie J. WeinsteinWendy CozenSusan M. GapsturMichael DeanPaolo BoffettaPaolo BoffettaPierluigi CoccoPaige M. BracciNicola J. CampAmy MooreHerve GhesquieresFederico CanzianJames MckayThomas M. HabermannNikolaus BeckerKari E. NorthDemetrius AlbanesAlain MonnereauMarc MaynadiéLesley F. TinkerChristine F. SkibolaVignesh RavichandranSusan L. SlagerKarin E. SmedbyKarin E. SmedbyRuth C. TravisJacqueline ClavelLucia MiligiMelissa C. SoutheyMary CarringtonClaire M. VajdicKaren CurtinDavid G. CoxRoel VermeulenElio RiboliEleanor KaneWeiyin ZhouNathaniel RothmanMitchell J. MachielaYolanda BenaventeAlan A. ArslanMeredith YeagerPaul BrennanTongzhang ZhengElisabete WeiderpassMoara MachadoQing LanAlpa V. PatelJames R. CerhanSonja I. BerndtNeil E. CaporasoSilvia De SanjoséStephen J. ChanockNicole Wong DooLauren R. TerasSara PiroLenka ForetovaChi GaoGilles SallesGilles SallesImmaculata De VivoImmaculata De VivoAlexandra NietersBengt GlimeliusSophia S. WangRichard K. SeversonMads MelbyeMads MelbyeHans-olov AdamiHans-olov AdamiHans-olov AdamiYawei ZhangCarolyn StewartLucia CondeBrenda M. BirmannAngela Brooks-wilsonAngela Brooks-wilsonThierry Jo MolinaKenneth OffitBrian K. LinkMartha GlennAnthony Stainessubject
GeneticsChronic lymphocytic leukemiadiffuse large B-cell lymphomaFollicular lymphomaSingle-nucleotide polymorphismRuns of HomozygosityBiologymedicine.diseasemarginal zone lymphomaArticlefollicular lymphomaimmune system diseaseshemic and lymphatic diseasesGenetic variationmedicinechronic lymphocytic leukemiahomozygosityDiffuse large B-cell lymphomaInbreedingNon-Hodgkin lymphomaGenetic associationdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-06-01 | Journal of Translational Genetics and Genomics |