Multiple myeloma (MM) is a blood malignancy originating from plasma cells. First-degree relatives of patients with MM have two- to four-fold higher risk of MM. However, the molecular basis remains largely unknown. This Ph.D. project aims to identify novel DNA sequence variants predisposing to MM through genome-wide association studies (GWAS) and, subsequently, characterize identified variants functionally.
Article I describes a systematic study where we screened for causal gene-regulatory variants at 21 MM risk loci. Article II describes a Nordic GWAS identifying the SOHLH2 (13q13.3) as a novel MM risk locus. Article III describes a novel international meta-analysis of GWAS data totalling 10 906 cases and 366 221 controls, identifying twelve new risk variants for MM accounted for by nine loci: 5q35.2 CPEB4, 6p22.2 BTN3A2, 9q21.33 DAPK1, 10q24.33 STN1, 10q25.2 MXI1, 19p13.3 NFIC, 21q11.2, SAMSN1 and a rare variant at 13q13.1 BRCA2. Finally, in Article IV, we explore the possibility of identifying transcription factors that mediate allele-specific gene-regulatory effects through combined use of CRISPR/Cas9 screening and epistasis analysis of gene expression data.
The work presented in this thesis provides new insight into the mechanisms underlying genetic predisposition for multiple myeloma.
- Department of Laboratory Medicine
- Nilsson, Björn, Supervisor
- Lopez de Lapuente Portilla, Aitzkoa, Supervisor
|Award date||2022 Oct 21|
|Place of Publication||Lund|
|Publication status||Published - 2022|
Place: Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/66575729066
Name: Trynka, Gosia
Title: Head of Immune Genomics Group, Wellcome Sanger Institute and Director of Experimental Sciences, Open Targets
Affiliation: Wellcome Sanger Institute, Open Targets
- multiple myeloma
- cancer genetics
- functional characterization
- Germline variants