Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
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 pe...
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doaj-921d6df1bf474729aae772a11dae54202020-11-25T03:49:15ZengBMCHuman Genomics1479-73642019-08-011311810.1186/s40246-019-0231-5Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genesMolly Went0Ben Kinnersley1Amit Sud2David C. Johnson3Niels Weinhold4Asta Försti5Mark van Duin6Giulia Orlando7Jonathan S. Mitchell8Rowan Kuiper9Brian A. Walker10Walter M. Gregory11Per Hoffmann12Graham H. Jackson13Markus M. Nöthen14Miguel Inacio da Silva Filho15Hauke Thomsen16Annemiek Broyl17Faith E. Davies18Unnur Thorsteinsdottir19Markus Hansson20Martin Kaiser21Pieter Sonneveld22Hartmut Goldschmidt23Kari Stefansson24Kari Hemminki25Björn Nilsson26Gareth J. Morgan27Richard S. Houlston28Division of Genetics and Epidemiology, The Institute of Cancer ResearchDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDivision of Molecular Pathology, The Institute of Cancer ResearchDepartment of Internal Medicine V, University of HeidelbergGerman Cancer Research CenterDepartment of Hematology, Erasmus MC Cancer InstituteDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDivision of Genetics and Epidemiology, The Institute of Cancer ResearchDepartment of Hematology, Erasmus MC Cancer InstituteMyeloma Institute for Research and Therapy, University of Arkansas for Medical SciencesClinical Trials Research Unit, University of LeedsInstitute of Human Genetics, University of BonnRoyal Victoria InfirmaryInstitute of Human Genetics, University of BonnGerman Cancer Research CenterGerman Cancer Research CenterDepartment of Hematology, Erasmus MC Cancer InstituteMyeloma Institute for Research and Therapy, University of Arkansas for Medical SciencesdeCODE GeneticsHematology Clinic, Skåne University HospitalDivision of Molecular Pathology, The Institute of Cancer ResearchMyeloma Institute for Research and Therapy, University of Arkansas for Medical SciencesDepartment of Internal Medicine V, University of HeidelbergdeCODE GeneticsGerman Cancer Research CenterHematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13Myeloma Institute for Research and Therapy, University of Arkansas for Medical SciencesDivision of Genetics and Epidemiology, The Institute of Cancer ResearchAbstract 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.http://link.springer.com/article/10.1186/s40246-019-0231-5Genome-wide association studyGene expressionMultiple myelomaTranscriptome-wide association study |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Molly Went Ben Kinnersley Amit Sud David C. Johnson Niels Weinhold Asta Försti Mark van Duin Giulia Orlando Jonathan S. Mitchell Rowan Kuiper Brian A. Walker Walter M. Gregory Per Hoffmann Graham H. Jackson Markus M. Nöthen Miguel Inacio da Silva Filho Hauke Thomsen Annemiek Broyl Faith E. Davies Unnur Thorsteinsdottir Markus Hansson Martin Kaiser Pieter Sonneveld Hartmut Goldschmidt Kari Stefansson Kari Hemminki Björn Nilsson Gareth J. Morgan Richard S. Houlston |
spellingShingle |
Molly Went Ben Kinnersley Amit Sud David C. Johnson Niels Weinhold Asta Försti Mark van Duin Giulia Orlando Jonathan S. Mitchell Rowan Kuiper Brian A. Walker Walter M. Gregory Per Hoffmann Graham H. Jackson Markus M. Nöthen Miguel Inacio da Silva Filho Hauke Thomsen Annemiek Broyl Faith E. Davies Unnur Thorsteinsdottir Markus Hansson Martin Kaiser Pieter Sonneveld Hartmut Goldschmidt Kari Stefansson Kari Hemminki Björn Nilsson Gareth J. Morgan Richard S. Houlston Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes Human Genomics Genome-wide association study Gene expression Multiple myeloma Transcriptome-wide association study |
author_facet |
Molly Went Ben Kinnersley Amit Sud David C. Johnson Niels Weinhold Asta Försti Mark van Duin Giulia Orlando Jonathan S. Mitchell Rowan Kuiper Brian A. Walker Walter M. Gregory Per Hoffmann Graham H. Jackson Markus M. Nöthen Miguel Inacio da Silva Filho Hauke Thomsen Annemiek Broyl Faith E. Davies Unnur Thorsteinsdottir Markus Hansson Martin Kaiser Pieter Sonneveld Hartmut Goldschmidt Kari Stefansson Kari Hemminki Björn Nilsson Gareth J. Morgan Richard S. Houlston |
author_sort |
Molly Went |
title |
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
title_short |
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
title_full |
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
title_fullStr |
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
title_full_unstemmed |
Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
title_sort |
transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes |
publisher |
BMC |
series |
Human Genomics |
issn |
1479-7364 |
publishDate |
2019-08-01 |
description |
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. |
topic |
Genome-wide association study Gene expression Multiple myeloma Transcriptome-wide association study |
url |
http://link.springer.com/article/10.1186/s40246-019-0231-5 |
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