TY  - JOUR
VL  - 13
ID  - heidok27019
PB  - Henry Stewart Publ.
AV  - public
IS  - 37
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/27019/
N2  - 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.
JF  - Human Genomics
CY  - London
EP  - 8
A1  - Went, Molly
A1  - Kinnersley, Ben
A1  - Sud, Amit
A1  - Johnson, David C.
A1  - Weinhold, Niels
A1  - Försti, Asta
A1  - van Duin, Mark
A1  - Orlando, Giulia
A1  - Mitchell, Jonathan S.
A1  - Kuiper, Rowan
A1  - Walker, Brian A.
A1  - Gregory, Walter M.
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Nöthen, Markus M.
A1  - da Silva Filho, Miguel Inacio
A1  - Thomsen, Hauke
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Thorsteinsdottir, Unnur
A1  - Hansson, Markus
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Goldschmidt, Hartmut
A1  - Stefansson, Kari
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Morgan, Gareth J.
A1  - Houlston, Richard S.
SP  - 1
Y1  - 2019///
TI  - Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
SN  - 1479-7364
KW  - Genome-wide association study
KW  -  Gene expression
KW  -  Multiplemyeloma
KW  -  Transcriptome-wide association study
ER  -