Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

• MeSH
• anotace sekvence MeSH
• genetická predispozice k nemoci * MeSH
• genotypizační techniky MeSH
• HEK293 buňky MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 14 genetika   MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• mikro RNA metabolismus   MeSH
• proliferace buněk MeSH
• reportérové geny MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• rodina MeSH
• sekvence nukleotidů MeSH
• typy dědičnosti genetika   MeSH
• Waldenströmova makroglobulinemie genetika   MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH