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

Authors:
Subhayan Chattopadhyay
Subhayan Chattopadhyay
School of Mathematics and Statistics
Islamabad | Pakistan
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Pankaj Yadav
Pankaj Yadav
Maulana Azad Institute of Dental Sciences
India
Niels Weinhold
Niels Weinhold
Institute of Cancer Research
United Kingdom
Markus M Nothen
Markus M Nothen
1] Institute of Human Genetics
Ahmedabad | India
Uta Bertsch
Uta Bertsch
University Hospital

Commun Biol 2019 4;2:89. Epub 2019 Mar 4.

1Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120 Germany.

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, T17 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.

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http://dx.doi.org/10.1038/s42003-019-0329-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399257PMC
March 2019
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