Genetic predisposition for Multiple Myeloma. Identification and functional characterization of risk variants
(2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- 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,... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/b1653bec-b5c8-4a10-8a24-e79faf120fbc
- author
- Duran Lozano, Laura LU
- supervisor
- opponent
-
- Head of Immune Genomics Group, Wellcome Sanger Institute and Director of Experimental Sciences, Open Targets Trynka, Gosia, Wellcome Sanger Institute, Open Targets
- organization
- publishing date
- 2022
- type
- Thesis
- publication status
- published
- subject
- keywords
- GWAS, multiple myeloma, CRISPR/Cas9, cancer genetics, functional characterization, Germline variants
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2022:132
- pages
- 89 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/66575729066
- defense date
- 2022-10-21 13:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-294-6
- language
- English
- LU publication?
- yes
- id
- b1653bec-b5c8-4a10-8a24-e79faf120fbc
- date added to LUP
- 2022-09-30 12:16:09
- date last changed
- 2022-10-04 16:04:56
@phdthesis{b1653bec-b5c8-4a10-8a24-e79faf120fbc,
abstract = {{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.<br/>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 <i>SOHLH2</i> (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 <i>CPEB4</i>, 6p22.2<i> BTN3A2</i>, 9q21.33 <i>DAPK1</i>, 10q24.33 <i>STN1</i>, 10q25.2 <i>MXI1</i>, 19p13.3 <i>NFIC</i>, 21q11.2, <i>SAMSN1</i> and a rare variant at 13q13.1 <i>BRCA2</i>. 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.<br/>The work presented in this thesis provides new insight into the mechanisms underlying genetic predisposition for multiple myeloma.}},
author = {{Duran Lozano, Laura}},
isbn = {{978-91-8021-294-6}},
issn = {{1652-8220}},
keywords = {{GWAS; multiple myeloma; CRISPR/Cas9; cancer genetics; functional characterization; Germline variants}},
language = {{eng}},
number = {{2022:132}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Genetic predisposition for Multiple Myeloma. Identification and functional characterization of risk variants}},
url = {{https://lup.lub.lu.se/search/files/125000864/LDL_kappa_covers_1022.pdf}},
year = {{2022}},
}