Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma

Research output: Contribution to journalArticle

Abstract

Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response.

Details

Authors
  • Subhayan Chattopadhyay
  • Hauke Thomsen
  • Pankaj Yadav
  • Miguel Inacio da Silva Filho
  • Niels Weinhold
  • Markus M Nöthen
  • Per Hoffman
  • Uta Bertsch
  • Stefanie Huhn
  • Gareth J Morgan
  • Hartmut Goldschmidt
  • Richard Houlston
  • Kari Hemminki
  • Asta Försti
Organisations
External organisations
  • German Cancer Research Centre
  • Heidelberg University
  • University Hospital Heidelberg
  • University of Arkansas
  • University of Bonn
  • University of Basel
  • National Centre of Tumor Diseases
  • Institute of Cancer Research London
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Article number89
JournalCommunications Biology
Volume2
Publication statusPublished - 2019 Mar 4
Publication categoryResearch
Peer-reviewedYes