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

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

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