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

Details

• Alternative Title:
  J Transl Genet Genom
• Personal Author:
  Moore, Amy ; Machiela, Mitchell J. ; Machado, Moara ; Wang, Sophia S. ; Kane, Eleanor ; Slager, Susan L. ; Zhou, Weiyin ; Carrington, Mary ; Lan, Qing ; Milne, Roger L. ; Birmann, Brenda M. ; Adami, Hans-Olov ; Albanes, Demetrius ; Arslan, Alan A. ; Becker, Nikolaus ; Benavente, Yolanda ; Bisanzi, Simonetta ; Boffetta, Paolo ; Bracci, Paige M. ; Brennan, Paul ; Brooks-Wilson, Angela R. ; Canzian, Federico ; Caporaso, Neil ; Clavel, Jacqueline ; Cocco, Pierluigi ; Conde, Lucia ; Cox, David G. ; Cozen, Wendy ; Curtin, Karen ; De Vivo, Immaculata ; de Sanjose, Silvia ; Foretova, Lenka ; Gapstur, Susan M. ; Ghesquières, Hervè ; Giles, Graham G. ; Glenn, Martha ; Glimelius, Bengt ; Gao, Chi ; Habermann, Thomas M. ; Hjalgrim, Henrik ; Jackson, Rebecca D. ; Liebow, Mark ; Link, Brian K. ; Maynadie, Marc ; McKay, James ; Melbye, Mads ; Miligi, Lucia ; Molina, Thierry J. ; Monnereau, Alain ; Nieters, Alexandra ; North, Kari E. ; Offit, Kenneth ; Patel, Alpa V. ; Piro, Sara ; Ravichandran, Vignesh ; Riboli, Elio ; Salles, Gilles ; Severson, Richard K. ; Skibola, Christine F. ; Smedby, Karin E. ; Southey, Melissa C. ; Spinelli, John J. ; Staines, Anthony ; Stewart, Carolyn ; Teras, Lauren R. ; Tinker, Lesley F. ; Travis, Ruth C. ; Vajdic, Claire M. ; Vermeulen, Roel C. H. ; Vijai, Joseph ; Weiderpass, Elisabete ; Weinstein, Stephanie ; Doo, Nicole Wong ; Zhang, Yawei ; Zheng, Tongzhang ; Chanock, Stephen J. ; Rothman, Nathaniel ; Cerhan, James R. ; Dean, Michael ; Camp, Nicola J. ; Yeager, Meredith ; Berndt, Sonja I.
• 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 × 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.
  
  
• Subjects:
  Article Chronic Lymphocytic Leukemia Diffuse Large B-cell Lymphoma Follicular Lymphoma Homozygosity Marginal Zone Lymphoma Non-Hodgkin Lymphoma
• Source:
  J Transl Genet Genom. 5:200-217
• Pubmed ID:
  34622145
• Pubmed Central ID:
  PMC8494431
• Document Type:
  Journal Article
• Funding:
  HHSN268201100046C/HL/NHLBI NIH HHSUnited States/ ; P30 ES000260/ES/NIEHS NIH HHSUnited States/ ; U58 DP000807/DP/NCCDPHP CDC HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; R01 CA134674/CA/NCI NIH HHSUnited States/ ; N01 PC067009/CN/NCI NIH HHSUnited States/ ; HHSN268201100001I/HL/NHLBI NIH HHSUnited States/ ; P30 CA016087/CA/NCI NIH HHSUnited States/ ; HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; N01 PC067010/PC/NCI NIH HHSUnited States/ ; R01 CA098122/CA/NCI NIH HHSUnited States/ ; U01 HG007033/HG/NHGRI NIH HHSUnited States/ ; P01 CA087969/CA/NCI NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; R01 CA134958/CA/NCI NIH HHSUnited States/ ; R21 CA165923/CA/NCI NIH HHSUnited States/ ; HHSN268201100004I/HL/NHLBI NIH HHSUnited States/ ; P30 CA086862/CA/NCI NIH HHSUnited States/ ; U01 CA167552/CA/NCI NIH HHSUnited States/ ; N01 PC067008/PC/NCI NIH HHSUnited States/ ; HHSN268201100003C/WH/WHI NIH HHSUnited States/ ; R01 CA148690/CA/NCI NIH HHSUnited States/ ; R01 CA154643/CA/NCI NIH HHSUnited States/ ; R01 CA062006/CA/NCI NIH HHSUnited States/ ; N01 PC065064/PC/NCI NIH HHSUnited States/ ; K08 CA134919/CA/NCI NIH HHSUnited States/ ; UL1 TR000135/TR/NCATS NIH HHSUnited States/ ; HHSN271201100004C/AG/NIA NIH HHSUnited States/ ; R01 CA098661/CA/NCI NIH HHSUnited States/ ; UM1 CA186107/CA/NCI NIH HHSUnited States/ ; HHSN268201100002C/WH/WHI NIH HHSUnited States/ ; P30 CA015083/CA/NCI NIH HHSUnited States/ ; R01 CA092153/CA/NCI NIH HHSUnited States/ ; ZIA CP010136/ImNIH/Intramural NIH HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; P50 CA097274/CA/NCI NIH HHSUnited States/ ; HHSN268201100003I/HL/NHLBI NIH HHSUnited States/ ; R01 CA049449/CA/NCI NIH HHSUnited States/ ; HHSN268201100002I/HL/NHLBI NIH HHSUnited States/ ; R01 CA200703/CA/NCI NIH HHSUnited States/ ; N01CO12400/CA/NCI NIH HHSUnited States/ ; HHSN261200800001C/RC/CCR NIH HHSUnited States/ ; U01 CA049449/CA/NCI NIH HHSUnited States/ ; R01 CA149445/CA/NCI NIH HHSUnited States/ ; HHSN261201000026C/CA/NCI NIH HHSUnited States/ ; HHSN268201100001C/WH/WHI NIH HHSUnited States/ ; HHSN268201100004C/WH/WHI NIH HHSUnited States/ ; U01 CA118444/CA/NCI NIH HHSUnited States/ ; HHSN261200800001E/CA/NCI NIH HHSUnited States/ ; P30 CA042014/CA/NCI NIH HHSUnited States/
• Volume:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5a46d712f31ad54d014b9b152ca5b5277155175e7feb0fb53f51eb759f6de551
• Download URL:
  https://stacks.cdc.gov/view/cdc/110635/cdc_110635_DS1.pdf
• File Type:
  [PDF - 543.78 KB ]