Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
Molly WentAmit SudAsta FörstiBritt-Marie HalvarssonNiels WeinholdScott KimberMark van DuinGudmar ThorleifssonAmy HolroydDavid C JohnsonNi LiGiulia OrlandoPhilip J LawMina AliBowang ChenJonathan S MitchellDaníel F GuðbjartssonRowan KuiperOwen W StephensUta BertschPeter BroderickChiara CampoObul Reddy BandapalliHermann EinseleWalter A GregoryUrban GullbergJens HillengassPer HoffmannGraham H JacksonKarl-Heinz JöckelEllinor JohnssonSigurður Y KristinssonUlf-Henrik MellqvistHareth NahiDouglas F EastonPaul David Peter PharoahAlison DunningJulian PetoFrederico CanzianAnthony SwerdlowRosalind A EelesZSofia Kote-JaraiKenneth Ross MuirNora PashayanJolanta NickelMarkus M NöthenThorunn RafnarFiona M RossMiguel Inacio da Silva FilhoHauke ThomsenIngemar TuressonAnnette VangstedNiels Frost AndersenAnders WaageBrian A WalkerAnna-Karin WihlborgAnnemiek BroylFaith E DaviesUnnur ThorsteinsdottirChristian LangerMarkus HanssonHartmut GoldschmidtMartin KaiserPieter SonneveldKari StefanssonGareth J MorganKari HemminkiBjörn NilssonRichard S Houlstonnull nullPublished in: Nature communications (2018)
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
Keyphrases
- genome wide association
- gene expression
- cell cycle
- genome wide association study
- multiple myeloma
- genome wide
- dna methylation
- transcription factor
- cell death
- endoplasmic reticulum stress
- cell proliferation
- electronic health record
- machine learning
- healthcare
- big data
- signaling pathway
- deep learning
- social media
- cell cycle arrest
- heat stress