TY  - JOUR
AU  - Ajore, Ram
AU  - Niroula, Abhishek
AU  - Pertesi, Maroulio
AU  - Cafaro, Caterina
AU  - Thodberg, Malte
AU  - Went, Molly
AU  - Bao, Erik L
AU  - Duran-Lozano, Laura
AU  - Lopez de Lapuente Portilla, Aitzkoa
AU  - Olafsdottir, Thorunn
AU  - Ugidos-Damboriena, Nerea
AU  - Magnusson, Olafur
AU  - Samur, Mehmet
AU  - Lareau, Caleb A
AU  - Halldorsson, Gisli H
AU  - Thorleifsson, Gudmar
AU  - Norddahl, Gudmundur L
AU  - Gunnarsdottir, Kristbjorg
AU  - Försti, Asta
AU  - Goldschmidt, Hartmut
AU  - Hemminki, Kari
AU  - van Rhee, Frits
AU  - Kimber, Scott
AU  - Sperling, Adam S
AU  - Kaiser, Martin
AU  - Anderson, Kenneth
AU  - Jonsdottir, Ingileif
AU  - Munshi, Nikhil
AU  - Rafnar, Thorunn
AU  - Waage, Anders
AU  - Weinhold, Niels
AU  - Thorsteinsdottir, Unnur
AU  - Sankaran, Vijay G
AU  - Stefansson, Kari
AU  - Houlston, Richard
AU  - Nilsson, Björn
TI  - Functional dissection of inherited non-coding variation influencing multiple myeloma risk.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2022-00077
SP  - 151
PY  - 2022
AB  - Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy.
LB  - PUB:(DE-HGF)16
C6  - pmid:35013207
DO  - DOI:10.1038/s41467-021-27666-x
UR  - https://inrepo02.dkfz.de/record/178451
ER  -