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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
- Mitchell, Jonathan S., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 4. |
- Rasche, Leo, et al.
(author)
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Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma
- 2017
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:1, s. 30-34
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Journal article (peer-reviewed)abstract
- 18F-Fluorodeoxyglucose (FDG)–positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging with background signal suppression (DWIBS) are 2 powerful functional imaging modalities in the evaluation of malignant plasma cell (PC) disease multiple myeloma (MM). Preliminary observations have suggested that MM patients with extensive disease according to DWIBS may be reported as being disease-free on FDG-PET (“PET false-negative”). The aim of this study was to describe the proportion of PET false-negativity in a representative set of 227 newly diagnosed MM patients with simultaneous assessment of FDG-PET and DWIBS, and to identify tumor-intrinsic features associated with this pattern. We found the incidence of PET false-negativity to be 11%. Neither tumor load–associated parameters, such as degree of bone marrow PC infiltration, nor the PC proliferation rate were associated with this subset. However, the gene coding for hexokinase-2, which catalyzes the first step of glycolysis, was significantly lower expressed in PET false-negative cases (5.3-fold change, P < .001) which provides a mechanistic explanation for this feature. In conclusion, we demonstrate a relevant number of patients with FDG-PET false-negative MM and a strong association between hexokinase-2 expression and this negativity: a finding which may also be relevant for clinical imaging of other hematological cancers.
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| 6. |
- Went, Molly, et al.
(author)
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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
- 2018
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In: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:1
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Journal article (peer-reviewed)abstract
- The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
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| 7. |
- Went, Molly, et al.
(author)
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Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
- 2019
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In: Human Genomics. - : Springer Science and Business Media LLC. - 1479-7364. ; 13:1
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Journal article (peer-reviewed)abstract
- BackgroundWhile 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).ResultsGWAS 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.ConclusionsOur 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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