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dc.contributor.authorda Silva Filho, MI
dc.contributor.authorFörsti, A
dc.contributor.authorWeinhold, N
dc.contributor.authorMeziane, I
dc.contributor.authorCampo, C
dc.contributor.authorHuhn, S
dc.contributor.authorNickel, J
dc.contributor.authorHoffmann, P
dc.contributor.authorNöthen, MM
dc.contributor.authorJöckel, K-H
dc.contributor.authorLandi, S
dc.contributor.authorMitchell, JS
dc.contributor.authorJohnson, D
dc.contributor.authorMorgan, GJ
dc.contributor.authorHoulston, R
dc.contributor.authorGoldschmidt, H
dc.contributor.authorJauch, A
dc.contributor.authorMilani, P
dc.contributor.authorMerlini, G
dc.contributor.authorRowcieno, D
dc.contributor.authorHawkins, P
dc.contributor.authorHegenbart, U
dc.contributor.authorPalladini, G
dc.contributor.authorWechalekar, A
dc.contributor.authorSchönland, SO
dc.contributor.authorHemminki, K
dc.date.accessioned2017-03-03T10:38:45Z
dc.date.issued2017-08
dc.identifier.citationLeukemia, 2017, 31 (8), pp. 1735 - 1742
dc.identifier.issn0887-6924
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/469
dc.identifier.eissn1476-5551
dc.identifier.doi10.1038/leu.2016.387
dc.description.abstractImmunoglobulin 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.
dc.formatPrint-Electronic
dc.format.extent1735 - 1742
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectAmyloidosis
dc.subjectGenetic Predisposition to Disease
dc.subjectCyclin D1
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectImmunoglobulin Light Chains
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.titleGenome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma.
dc.typeJournal Article
dcterms.dateAccepted2016-11-30
rioxxterms.versionofrecord10.1038/leu.2016.387
rioxxterms.licenseref.startdate2017-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfLeukemia
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.volume31
pubs.embargo.termsNot known
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorJohnson, Daviden


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