TY  - JOUR
A1  - Mitchell, Jonathan S.
A1  - Li, Ni
A1  - Weinhold, Niels
A1  - Försti, Asta
A1  - Ali, Mina
A1  - van Duin, Mark
A1  - Thorleifsson, Gudmar
A1  - Johnson, David C.
A1  - Chen, Bowang
A1  - Halvarsson, Britt-Marie
A1  - Gudbjartsson, Daniel F.
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Campo, Chiara
A1  - Einsele, Hermann
A1  - Gregory, Walter A.
A1  - Gullberg, Urban
A1  - Henrion, Marc
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Johnsson, Ellinor
A1  - Jöud, Magnus
A1  - Kristinsson, Sigurdur Y.
A1  - Lenhoff, Stig
A1  - Lenive, Oleg
A1  - Mellqvist, Ulf-Henrik
A1  - Migliorini, Gabriele
A1  - Nahi, Hareth
A1  - Nelander, Sven
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - Rafnar, Thorunn
A1  - Ross, Fiona M.
A1  - da Silva Filho, Miguel Inacio
A1  - Swaminathan, Bhairavi
A1  - Thomsen, Hauke
A1  - Turesson, Ingemar
A1  - Vangsted, Annette
A1  - Vogel, Ulla
A1  - Waage, Anders
A1  - Walker, Brian A.
A1  - Wihlborg, Anna-Karin
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Thorsteinsdottir, Unnur
A1  - Langer, Christian
A1  - Hansson, Markus
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Stefansson, Kari
A1  - Morgan, Gareth J.
A1  - Goldschmidt, Hartmut
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Houlston, Richard S.
T1  - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
JF  - Nature Communications
N2  - 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 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 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.
KW  - Cancer genetics
KW  - Genome-wide association studies
KW  - Myeloma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983
VL  - 7
ER  - 
TY  - JOUR
A1  - Westbury, Sarah K
A1  - Turro, Ernest
A1  - Greene, Daniel
A1  - Lentaigne, Claire
A1  - Kelly, Anne M
A1  - Bariana, Tadbir K
A1  - Simeoni, Ilenia
A1  - Pillois, Xavier
A1  - Attwood, Antony
A1  - Austin, Steve
A1  - Jansen, Sjoert BG
A1  - Bakchoul, Tamam
A1  - Crisp-Hihn, Abi
A1  - Erber, Wendy N
A1  - Favier, Rémi
A1  - Foad, Nicola
A1  - Gattens, Michael
A1  - Jolley, Jennifer D
A1  - Liesner, Ri
A1  - Meacham, Stuart
A1  - Millar, Carolyn M
A1  - Nurden, Alan T
A1  - Peerlinck, Kathelijne
A1  - Perry, David J
A1  - Poudel, Pawan
A1  - Schulman, Sol
A1  - Schulze, Harald
A1  - Stephens, Jonathan C
A1  - Furie, Bruce
A1  - Robinson, Peter N
A1  - van Geet, Chris
A1  - Rendon, Augusto
A1  - Gomez, Keith
A1  - Laffan, Michael A
A1  - Lambert, Michele P
A1  - Nurden, Paquita
A1  - Ouwehand, Willem H
A1  - Richardson, Sylvia
A1  - Mumford, Andrew D
A1  - Freson, Kathleen
T1  - Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders
JF  - Genome Medicine
N2  - Background: 
Heritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases. 
Methods: 
We report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms. Cluster analyses are then used to characterise groups of cases with similar HPO terms and variants in the same genes. Results: 
We show that 60% of index cases with heritable BPD enrolled at 10 European or US centres were annotated with HPO terms indicating abnormalities in organ systems other than blood or blood-forming tissues, particularly the nervous system. Cases within pedigrees clustered closely together on the bases of their HPO-coded phenotypes, as did cases sharing several clinically suspected syndromic disorders. Cases subsequently found to harbour variants in ACTN1 also clustered closely, even though diagnosis of this recently described disorder was not possible using only the clinical and laboratory data available to the enrolling clinician. 
Conclusions: 
These findings validate our novel HPO-based phenotype clustering methodology for known BPD, thus providing a new discovery tool for BPD of unknown genetic basis. This approach will also be relevant for other rare diseases with significant genetic heterogeneity.
KW  - disease
KW  - thrombocytopenia
KW  - guidelines
KW  - complex
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143329
VL  - 7
IS  - 36
ER  - 
TY  - JOUR
A1  - Went, Molly
A1  - Sud, Amit
A1  - Speedy, Helen
A1  - Sunter, Nicola J.
A1  - Försti, Asta
A1  - Law, Philip J.
A1  - Johnson, David C.
A1  - Mirabella, Fabio
A1  - Holroyd, Amy
A1  - Li, Ni
A1  - Orlando, Giulia
A1  - Weinhold, Niels
A1  - van Duin, Mark
A1  - Chen, Bowang
A1  - Mitchell, Jonathan S.
A1  - Mansouri, Larry
A1  - Juliusson, Gunnar
A1  - Smedby, Karin E
A1  - Jayne, Sandrine
A1  - Majid, Aneela
A1  - Dearden, Claire
A1  - Allsup, David J.
A1  - Bailey, James R.
A1  - Pratt, Guy
A1  - Pepper, Chris
A1  - Fegan, Chris
A1  - Rosenquist, Richard
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Einsele, Hermann
A1  - Gregory, Walter M.
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Jöckel, Karl-Heinz
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - da Silva Filho, Miguel Inacio
A1  - Thomsen, Hauke
A1  - Walker, Brian A.
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Hansson, Markus
A1  - Goldschmidt, Hartmut
A1  - Dyer, Martin J. S.
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Morgan, Gareth J.
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Catovsky, Daniel
A1  - Allan, James M.
A1  - Houlston, Richard S.
T1  - Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
JF  - Blood Cancer Journal
N2  - 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.
KW  - cancer genetics
KW  - myeloma
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233627
VL  - 9
ER  -