Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Jonathan S Mitchell; Ni Li; Niels Weinhold; Asta Försti; Mina Ali; Mark van Duin; Gudmar Thorleifsson; D C Johnson; B. Chen; Britt-Marie Halvarsson; Daniel F Gudbjartsson; Rowan Kuiper; Owen W Stephens; Uta Bertsch; Peter Broderick; Chiara Campo; Hermann Einsele; Walter A Gregory; Urban Gullberg; Marc Henrion; Jens Hillengass; Per Hoffmann; Graham H Jackson; Ellinor Johnsson; Magnus Jöud; Sigurður Y Kristinsson; Stig Lenhoff; Oleg Lenive; Ulf-Henrik Mellqvist; Gabriele Migliorini; Hareth Nahi; Sven Nelander; Jolanta Nickel; Markus M Nöthen; Thorunn Rafnar; Fiona M Ross; M.I. da Silva Filho; Bhairavi Swaminathan; H. Thomsen; Ingemar Turesson; Annette Vangsted; Ulla Vogel; Anders Waage; Brian A Walker; Anna-Karin Wihlborg; Annemiek Broyl; Faith E Davies; Unnur Thorsteinsdottir; Christian Langer; Markus Hansson; Martin Kaiser; Pieter Sonneveld; Kari Stefansson; Gareth J Morgan; Hartmut Goldschmidt; Kari Hemminki; Björn Nilsson; Richard S Houlston

doi:10.1038/ncomms12050

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Jonathan S Mitchell, Ni Li, Niels Weinhold, Asta Försti, Mina Ali, Mark van Duin, Gudmar Thorleifsson, D C Johnson, B. Chen, Britt-Marie Halvarsson, Daniel F Gudbjartsson, Rowan Kuiper, Owen W Stephens, Uta Bertsch, Peter Broderick, Chiara Campo, Hermann Einsele, Walter A Gregory, Urban Gullberg, Marc HenrionJens Hillengass, Per Hoffmann, Graham H Jackson, Ellinor Johnsson, Magnus Jöud, Sigurður Y Kristinsson, Stig Lenhoff, Oleg Lenive, Ulf-Henrik Mellqvist, Gabriele Migliorini, Hareth Nahi, Sven Nelander, Jolanta Nickel, Markus M Nöthen, Thorunn Rafnar, Fiona M Ross, M.I. da Silva Filho, Bhairavi Swaminathan, H. Thomsen, Ingemar Turesson, Annette Vangsted, Ulla Vogel, Anders Waage, Brian A Walker, Anna-Karin Wihlborg, Annemiek Broyl, Faith E Davies, Unnur Thorsteinsdottir, Christian Langer, Markus Hansson, Martin Kaiser, Pieter Sonneveld, Kari Stefansson, Gareth J Morgan, Hartmut Goldschmidt, Kari Hemminki, Björn Nilsson, Richard S Houlston

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Artikelnummer	12050
Tidskrift	Nature Communications
Volym	7
DOI	https://doi.org/10.1038/ncomms12050
Status	Published - 2016

Ämnesklassifikation (UKÄ)

Cancer och onkologi

FN:s Globala mål

Denna forskningsoutput relaterar till följande Globala mål

Tillgång till dokument

10.1038/ncomms12050

2 Doktorsavhandling (sammanläggning)

Genetic Predisposition to Sporadic and Familial Multiple Myeloma
Bidragets översatta titel : Genetisk predisposition för sporadiskt och familjärt multipelt myelom Halvarsson, B-M., 2022, Lund: Lund University, Faculty of Medicine. 99 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Öppen tillgång
Fil
Identification and characterization of DNA sequence variants associated with multiple myeloma
Ali, M., 2018, Lund: Lund University: Faculty of Medicine. 49 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

1 Aktiva

Genetic predisposition for multiple myeloma
Nilsson, B., Pertesi, M., Ajore, R., Wihlborg, A., Duran Lozano, L., Cafaro, C., Johnsson, E., Hansson, M., Halvarsson, B. & Niroula, A.
2011/01/03 → …
Projekt: Forskning

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Mitchell, J. S., Li, N., Weinhold, N., Försti, A., Ali, M., van Duin, M., Thorleifsson, G., Johnson, D. C., Chen, B., Halvarsson, B.-M., Gudbjartsson, D. F., Kuiper, R., Stephens, O. W., Bertsch, U., Broderick, P., Campo, C., Einsele, H., Gregory, W. A., Gullberg, U., ... Houlston, R. S. (2016). Genome-wide association study identifies multiple susceptibility loci for multiple myeloma. Nature Communications, 7, Artikel 12050. https://doi.org/10.1038/ncomms12050

@article{44e94020f8674d82818d39eb100d6a67,

title = "Genome-wide association study identifies multiple susceptibility loci for multiple myeloma",

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 × 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.",

author = "Mitchell, {Jonathan S} and Ni Li and Niels Weinhold and Asta F{\"o}rsti and Mina Ali and {van Duin}, Mark and Gudmar Thorleifsson and Johnson, {D C} and B. Chen and Britt-Marie Halvarsson and Gudbjartsson, {Daniel F} and Rowan Kuiper and Stephens, {Owen W} and Uta Bertsch and Peter Broderick and Chiara Campo and Hermann Einsele and Gregory, {Walter A} and Urban Gullberg and Marc Henrion and Jens Hillengass and Per Hoffmann and Jackson, {Graham H} and Ellinor Johnsson and Magnus J{\"o}ud and Kristinsson, {Sigur{\dh}ur Y} and Stig Lenhoff and Oleg Lenive and Ulf-Henrik Mellqvist and Gabriele Migliorini and Hareth Nahi and Sven Nelander and Jolanta Nickel and N{\"o}then, {Markus M} and Thorunn Rafnar and Ross, {Fiona M} and {da Silva Filho}, M.I. and Bhairavi Swaminathan and H. Thomsen and Ingemar Turesson and Annette Vangsted and Ulla Vogel and Anders Waage and Walker, {Brian A} and Anna-Karin Wihlborg and Annemiek Broyl and Davies, {Faith E} and Unnur Thorsteinsdottir and Christian Langer and Markus Hansson and Martin Kaiser and Pieter Sonneveld and Kari Stefansson and Morgan, {Gareth J} and Hartmut Goldschmidt and Kari Hemminki and Bj{\"o}rn Nilsson and Houlston, {Richard S}",

year = "2016",

doi = "10.1038/ncomms12050",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Mitchell, JS, Li, N, Weinhold, N, Försti, A, Ali, M, van Duin, M, Thorleifsson, G, Johnson, DC, Chen, B, Halvarsson, B-M, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Einsele, H, Gregory, WA, Gullberg, U, Henrion, M, Hillengass, J, Hoffmann, P, Jackson, GH, Johnsson, E, Jöud, M, Kristinsson, SY, Lenhoff, S, Lenive, O, Mellqvist, U-H, Migliorini, G, Nahi, H, Nelander, S, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Swaminathan, B, Thomsen, H, Turesson, I, Vangsted, A, Vogel, U, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Goldschmidt, H, Hemminki, K , Nilsson, B & Houlston, RS 2016, 'Genome-wide association study identifies multiple susceptibility loci for multiple myeloma', Nature Communications, vol. 7, 12050. https://doi.org/10.1038/ncomms12050

TY - JOUR

T1 - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

AU - Mitchell, Jonathan S

AU - Li, Ni

AU - Weinhold, Niels

AU - Försti, Asta

AU - Ali, Mina

AU - van Duin, Mark

AU - Thorleifsson, Gudmar

AU - Johnson, D C

AU - Chen, B.

AU - Halvarsson, Britt-Marie

AU - Gudbjartsson, Daniel F

AU - Kuiper, Rowan

AU - Stephens, Owen W

AU - Bertsch, Uta

AU - Broderick, Peter

AU - Campo, Chiara

AU - Einsele, Hermann

AU - Gregory, Walter A

AU - Gullberg, Urban

AU - Henrion, Marc

AU - Hillengass, Jens

AU - Hoffmann, Per

AU - Jackson, Graham H

AU - Johnsson, Ellinor

AU - Jöud, Magnus

AU - Kristinsson, Sigurður Y

AU - Lenhoff, Stig

AU - Lenive, Oleg

AU - Mellqvist, Ulf-Henrik

AU - Migliorini, Gabriele

AU - Nahi, Hareth

AU - Nelander, Sven

AU - Nickel, Jolanta

AU - Nöthen, Markus M

AU - Rafnar, Thorunn

AU - Ross, Fiona M

AU - da Silva Filho, M.I.

AU - Swaminathan, Bhairavi

AU - Thomsen, H.

AU - Turesson, Ingemar

AU - Vangsted, Annette

AU - Vogel, Ulla

AU - Waage, Anders

AU - Walker, Brian A

AU - Wihlborg, Anna-Karin

AU - Broyl, Annemiek

AU - Davies, Faith E

AU - Thorsteinsdottir, Unnur

AU - Langer, Christian

AU - Hansson, Markus

AU - Kaiser, Martin

AU - Sonneveld, Pieter

AU - Stefansson, Kari

AU - Morgan, Gareth J

AU - Goldschmidt, Hartmut

AU - Hemminki, Kari

AU - Nilsson, Björn

AU - Houlston, Richard S

PY - 2016

Y1 - 2016

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.

AB - 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.

U2 - 10.1038/ncomms12050

DO - 10.1038/ncomms12050

M3 - Article

C2 - 27363682

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 12050

ER -

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

Sammanfattning

Ämnesklassifikation (UKÄ)

FN:s Globala mål

Tillgång till dokument

Fingeravtryck

Forskningsoutput

Genetic Predisposition to Sporadic and Familial Multiple Myeloma

Identification and characterization of DNA sequence variants associated with multiple myeloma

Projekt

Genetic predisposition for multiple myeloma

Citera det här