Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
Posted on 2019-08-21 - 04:28
Abstract 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.
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Went, Molly; Kinnersley, Ben; Sud, Amit; Johnson, David; Weinhold, Niels; Försti, Asta; et al. (2019). Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4638008.v1
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AUTHORS (29)
MW
Molly Went
BK
Ben Kinnersley
AS
Amit Sud
DJ
David Johnson
NW
Niels Weinhold
AF
Asta Försti
MD
Mark Duin
GO
Giulia Orlando
JM
Jonathan Mitchell
RK
Rowan Kuiper
BW
Brian Walker
WG
Walter Gregory
PH
Per Hoffmann
GJ
Graham Jackson
MN
Markus Nöthen
MS
Miguel Silva Filho
HT
Hauke Thomsen
AB
Annemiek Broyl
FD
Faith Davies
UT
Unnur Thorsteinsdottir