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

Chattopadhyay, SubhayanGerman Cancer Research Centre,Heidelberg University (författare)

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.

Thomsen, HaukeGerman Cancer Research Centre(Swepub:lu)med-hth (författare)
Yadav, PankajGerman Cancer Research Centre (författare)
da Silva Filho, Miguel InacioGerman Cancer Research Centre(Swepub:lu)med-md_ (författare)
Weinhold, NielsUniversity of Arkansas,University Hospital Heidelberg (författare)
Nöthen, Markus MUniversity of Bonn (författare)
Hoffman, PerUniversity of Bonn,University of Basel (författare)
Bertsch, UtaUniversity Hospital Heidelberg (författare)
Huhn, StefanieUniversity Hospital Heidelberg (författare)
Morgan, Gareth JUniversity of Arkansas (författare)
Goldschmidt, HartmutUniversity Hospital Heidelberg,National Centre of Tumor Diseases (författare)
Houlston, RichardInstitute of Cancer Research London (författare)
Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre(Swepub:lu)med-khk (författare)
Försti, AstaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre(Swepub:lu)med-asf (författare)
German Cancer Research CentreHeidelberg University (creator_code:org_t)

Ingår i:Communications Biology: Springer Science and Business Media LLC2:12399-3642

Av författaren/redakt...: Chattopadhyay, S ...; Thomsen, Hauke; Yadav, Pankaj; da Silva Filho, ...; Weinhold, Niels; Nöthen, Markus M; visa fler...; Hoffman, Per; Bertsch, Uta; Huhn, Stefanie; Morgan, Gareth J; Goldschmidt, Har ...; Houlston, Richar ...; Hemminki, Kari; Försti, Asta; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

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