Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

van Duin M; Halvarsson BM; Dunning A; Gullberg U; Kuiper R; Morgans GJ; Einsele H; Pashayan N; Chen BW; Andersen NF; Ross FM; Peto J; Thorleifsson G; Rafnar T; Kristinsson SY; Johnsson E; Nickel J; Swerdlow A; Pharoah P; Wihlborg AK; Gudbjartsson DF; Kaiser M; Johnson DC; Broyl A; Li N; Houlston RS; Filho MID; Canzian F; Sud A; Mitchell JS; Forsti A; Sonneveld P; Easton D; Hillengass J; Davies FE; Nothen MM; Houlston RS; Group Author(s): PRACTICAL Consortium; Kimber S; Jockel KH; Langer C; Muir K; Law PJ; Mellqvist UH; Vangsted A; Bertsch U; Hemminki K; Went M; Campo C; Turesson I; Waage A; Broderick P; Holroydl A; Hoffmann P; Jackson GH; Gregory WA; Stefansson K; Bandapalli OR; Orlando G; Nilsson B; Stephens OW; Eeles RA; Ali M; Hansson M; Thomsen H; Kote-Jarai Z; Walker BA; Nahi H; Goldschmidt H; Thorsteinsdottir U; Weinhold N
Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

van Duin M
Halvarsson BM
Dunning A
Gullberg U
Kuiper R
Morgans GJ
Einsele H
Pashayan N
Chen BW
Andersen NF
Ross FM
Peto J
Thorleifsson G
Rafnar T
Kristinsson SY
Johnsson E
Nickel J
Swerdlow A
Pharoah P
Wihlborg AK
Gudbjartsson DF
Kaiser M
Johnson DC
Broyl A
Li N
Houlston RS
Filho MID
Canzian F
Sud A
Mitchell JS
Forsti A
Sonneveld P
Easton D
Hillengass J
Davies FE
Nothen MM
Houlston RS; Group Author(s): PRACTICAL Consortium
Kimber S
Jockel KH
Langer C
Muir K
Law PJ
Mellqvist UH
Vangsted A
Bertsch U
Hemminki K
Went M
Campo C
Turesson I
Waage A
Broderick P
Holroydl A
Hoffmann P
Jackson GH
Gregory WA
Stefansson K
Bandapalli OR
Orlando G
Nilsson B
Stephens OW
Eeles RA
Ali M
Hansson M
Thomsen H
Kote-Jarai Z
Walker BA
Nahi H
Goldschmidt H
Thorsteinsdottir U
Weinhold N
Katso/Avaa
Lataukset: 

NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-04989-w
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042719908
Tiivistelmä
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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