Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

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http://hdl.handle.net/10138/299705

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Waldenström macroglobulinemia Group 2018 , ' Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia ' , Nature Communications , vol. 9 , no. 1 . https://doi.org/10.1038/s41467-018-06541-2

Title: Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
Author: Waldenström macroglobulinemia Group
Date: 2018
Language: eng
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/299705
Abstract: 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. © 2018, The Author(s).
Subject: enhanced green fluorescent protein
green fluorescent protein
microRNA
cell proliferation
chromosome 14
chromosome 6
family
genetic predisposition
genetics
genotyping technique
HEK293 cell line
human
inheritance
metabolism
molecular genetics
nucleotide sequence
reporter gene
reproducibility
risk factor
single nucleotide polymorphism
Waldenstroem macroglobulinemia
Base Sequence
Cell Proliferation
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 6
Family
Genes, Reporter
Genetic Predisposition to Disease
Genotyping Techniques
Green Fluorescent Proteins
HEK293 Cells
Humans
Inheritance Patterns
MicroRNAs
Molecular Sequence Annotation
Polymorphism, Single Nucleotide
Reproducibility of Results
Risk Factors
Waldenstrom Macroglobulinemia
1184 Genetics, developmental biology, physiology
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