title: Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
creator: Went, Molly
creator: Kinnersley, Ben
creator: Sud, Amit
creator: Johnson, David C.
creator: Weinhold, Niels
creator: Försti, Asta
creator: van Duin, Mark
creator: Orlando, Giulia
creator: Mitchell, Jonathan S.
creator: Kuiper, Rowan
creator: Walker, Brian A.
creator: Gregory, Walter M.
creator: Hoffmann, Per
creator: Jackson, Graham H.
creator: Nöthen, Markus M.
creator: da Silva Filho, Miguel Inacio
creator: Thomsen, Hauke
creator: Broyl, Annemiek
creator: Davies, Faith E.
creator: Thorsteinsdottir, Unnur
creator: Hansson, Markus
creator: Kaiser, Martin
creator: Sonneveld, Pieter
creator: Goldschmidt, Hartmut
creator: Stefansson, Kari
creator: Hemminki, Kari
creator: Nilsson, Björn
creator: Morgan, Gareth J.
creator: Houlston, Richard S.
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Background: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).    Results: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80–491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus.    Conclusions: Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.
publisher: Henry Stewart Publ.
date: 2019
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/27019/1/40246_2019_Article_231.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-270195
identifier:   Went, Molly ; Kinnersley, Ben ; Sud, Amit ; Johnson, David C. ; Weinhold, Niels ; Försti, Asta ; van Duin, Mark ; Orlando, Giulia ; Mitchell, Jonathan S. ; Kuiper, Rowan ; Walker, Brian A. ; Gregory, Walter M. ; Hoffmann, Per ; Jackson, Graham H. ; Nöthen, Markus M. ; da Silva Filho, Miguel Inacio ; Thomsen, Hauke ; Broyl, Annemiek ; Davies, Faith E. ; Thorsteinsdottir, Unnur ; Hansson, Markus ; Kaiser, Martin ; Sonneveld, Pieter ; Goldschmidt, Hartmut ; Stefansson, Kari ; Hemminki, Kari ; Nilsson, Björn ; Morgan, Gareth J. ; Houlston, Richard S.  (2019) Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.  Human Genomics, 13 (37).  pp. 1-8.  ISSN 1479-7364     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/27019/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng