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Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma

da Silva Filho, MI; Försti, A; Weinhold, N; Meziane, I; Campo, C; Huhn, S; Nickel, J; ... Hemminki, K; + view all (2017) Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma. Leukemia , 31 (8) pp. 1735-1742. 10.1038/leu.2016.387. Green open access

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Abstract

Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used. For AL amyloidosis, single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at P<10(-5) with homogeneity of results from the 3 sample sets; some of these were previously documented to influence MM risk, including the SNP at the IRF4 binding site. In AL amyloidosis, rs9344 at the splice site of cyclin D1, promoting translocation (11;14), reached the highest significance, P=7.80 × 10(-11); the SNP was only marginally significant in MM. SNP rs79419269 close to gene SMARCD3 involved in chromatin remodeling was also significant (P=5.2 × 10(-8)). These data provide evidence for common genetic susceptibility to AL amyloidosis and MM. Cyclin D1 is a more prominent driver in AL amyloidosis than in MM, but the links to aggregation of light chains need to be demonstrated.

Type: Article
Title: Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/leu.2016.387
Publisher version: http://doi.org/10.1038/leu.2016.387
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1549271
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