Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

Daniel Chubb; Niels Weinhold; Peter Broderick; Bowang Chen; David C Johnson; Asta Försti; Jayaram Vijayakrishnan; Gabriele Migliorini; Sara E Dobbins; Amy Holroyd; Dirk Hose; Brian A Walker; Faith E Davies; Walter A Gregory; Graham H Jackson; Julie A Irving; Guy Pratt; Chris Fegan; James Al Fenton; Kai Neben; Per Hoffmann; Markus M Nöthen; Thomas W Mühleisen; Lewin Eisele; Fiona M Ross; Christian Straka; Hermann Einsele; Christian Langer; Elisabeth Dörner; James M Allan; Anna Jauch; Gareth J Morgan; Kari Hemminki; Richard S Houlston; Hartmut Goldschmidt

doi:10.1038/ng.2733

Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

Nat Genet. 2013 Oct;45(10):1221-1225. doi: 10.1038/ng.2733. Epub 2013 Aug 18.

Authors

Daniel Chubb^#¹, Niels Weinhold^#², Peter Broderick¹, Bowang Chen³, David C Johnson⁴, Asta Försti^{3

5}, Jayaram Vijayakrishnan¹, Gabriele Migliorini¹, Sara E Dobbins¹, Amy Holroyd¹, Dirk Hose^{2

6}, Brian A Walker⁴, Faith E Davies⁴, Walter A Gregory⁷, Graham H Jackson⁸, Julie A Irving⁹, Guy Pratt¹⁰, Chris Fegan¹¹, James Al Fenton¹², Kai Neben², Per Hoffmann^{13

14}, Markus M Nöthen^{13

14

15}, Thomas W Mühleisen^{13

14}, Lewin Eisele¹⁶, Fiona M Ross¹⁷, Christian Straka¹⁸, Hermann Einsele¹⁹, Christian Langer²⁰, Elisabeth Dörner², James M Allan⁹, Anna Jauch²¹, Gareth J Morgan⁴, Kari Hemminki^{3

5}, Richard S Houlston¹, Hartmut Goldschmidt^{2

6}

Affiliations

¹ Division of Genetics and Epidemiology, Institute of Cancer Research, Surrey, UK.
² Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
³ German Cancer Research Center, Heidelberg, Germany.
⁴ Haemato-Oncology, Division of Pathology, Institute of Cancer Research, Surrey, UK.
⁵ Center for Primary Health Care Research, Lund University, Malmo, Sweden.
⁶ National Centre of Tumour Diseases, Heidelberg, Germany.
⁷ University of Leeds, Leeds, UK.
⁸ Royal Victoria Infirmary, Newcastle upon Tyne, UK.
⁹ Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle-upon-Tyne, UK.
¹⁰ Department of Haematology, Birmingham Heartlands Hospital, Birmingham, UK.
¹¹ Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
¹² Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹³ Institute of Human Genetics, University of Bonn, Germany.
¹⁴ Department of Genomics, University of Bonn, Germany.
¹⁵ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁶ Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University Duisburg-Essen, Germany.
¹⁷ Cytogenetics Group, Wessex Regional Cytogenetic Laboratory, Salisbury, UK.
¹⁸ Schön Klinik Starnberger See, Berg, Germany.
¹⁹ University Clinic of Würzburg, Würzburg, Germany.
²⁰ Department of Internal Medicine III, University of Ulm, Ulm, Germany.
²¹ Institute of Human Genetics, University of Heidelberg, Germany.

^# Contributed equally.

PMID: 23955597
PMCID: PMC5053356
DOI: 10.1038/ng.2733

Abstract

To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 individuals with multiple myeloma (cases) and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P = 8.70 × 10(-14)), 6p21.33 (rs2285803, PSORS1C2, P = 9.67 × 10(-11)), 17p11.2 (rs4273077, TNFRSF13B, P = 7.67 × 10(-9)) and 22q13.1 (rs877529, CBX7, P = 7.63 × 10(-16)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy, as well as insight into the biological basis of predisposition.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Case-Control Studies
Chromosome Aberrations*
Chromosomes, Human*
Genetic Predisposition to Disease*
Humans
Multiple Myeloma / genetics*

Abstract

Publication types

MeSH terms

Grants and funding