eprintid: 27019 rev_number: 13 eprint_status: archive userid: 1589 dir: disk0/00/02/70/19 datestamp: 2019-08-28 08:53:28 lastmod: 2019-10-18 13:42:36 status_changed: 2019-08-28 08:53:28 type: article metadata_visibility: show creators_name: Went, Molly creators_name: Kinnersley, Ben creators_name: Sud, Amit creators_name: Johnson, David C. creators_name: Weinhold, Niels creators_name: Försti, Asta creators_name: van Duin, Mark creators_name: Orlando, Giulia creators_name: Mitchell, Jonathan S. creators_name: Kuiper, Rowan creators_name: Walker, Brian A. creators_name: Gregory, Walter M. creators_name: Hoffmann, Per creators_name: Jackson, Graham H. creators_name: Nöthen, Markus M. creators_name: da Silva Filho, Miguel Inacio creators_name: Thomsen, Hauke creators_name: Broyl, Annemiek creators_name: Davies, Faith E. creators_name: Thorsteinsdottir, Unnur creators_name: Hansson, Markus creators_name: Kaiser, Martin creators_name: Sonneveld, Pieter creators_name: Goldschmidt, Hartmut creators_name: Stefansson, Kari creators_name: Hemminki, Kari creators_name: Nilsson, Björn creators_name: Morgan, Gareth J. creators_name: Houlston, Richard S. title: Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes subjects: ddc-610 divisions: i-850300 divisions: i-910100 keywords: Genome-wide association study, Gene expression, Multiplemyeloma, Transcriptome-wide association study 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. date: 2019 publisher: Henry Stewart Publ. id_scheme: DOI ppn_swb: 1678878189 own_urn: urn:nbn:de:bsz:16-heidok-270195 language: eng bibsort: WENTMOLLYTRANSCRIPT2019 full_text_status: public publication: Human Genomics volume: 13 number: 37 place_of_pub: London pagerange: 1-8 issn: 1479-7364 citation: 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 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/27019/1/40246_2019_Article_231.pdf