Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.
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Date
2019-08-20Author
Went, M
Kinnersley, B
Sud, A
Johnson, DC
Weinhold, N
Försti, A
van Duin, M
Orlando, G
Mitchell, JS
Kuiper, R
Walker, BA
Gregory, WM
Hoffmann, P
Jackson, GH
Nöthen, MM
da Silva Filho, MI
Thomsen, H
Broyl, A
Davies, FE
Thorsteinsdottir, U
Hansson, M
Kaiser, M
Sonneveld, P
Goldschmidt, H
Stefansson, K
Hemminki, K
Nilsson, B
Morgan, GJ
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Humans
Multiple Myeloma
Genetic Predisposition to Disease
Aminohydrolases
Cytidine Deaminase
Cytosine Deaminase
Gene Expression Profiling
Genotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Genome-Wide Association Study
Transcriptome
APOBEC-3G Deaminase
Research team
Cancer Genomics
Myeloma Group
Language
eng
Date accepted
2019-08-12
License start date
2019-08-20
Citation
Human genomics, 2019, 13 (1), pp. 37 - ?
Publisher
BMC