Genomewide association study on monoclonal gammopathy of unknown significance (MGUS)

被引：16

作者：

Thomsen, Hauke ^{[1
]}

Campo, Chiara ^{[1
]}

Weinhold, Niels ^{[2
,3
]}

da Silva Filho, Miguel Inacio ^{[1
]}

Pour, Ludek ^{[4
]}

Gregora, Evzen ^{[5
]}

Vodicka, Pavel ^{[6
,7
]}

Vodickova, Ludmila ^{[6
,7
,8
,9
]}

Hoffmann, Per ^{[10
,11
]}

Noethen, Markus M. ^{[10
,12
]}

Joeckel, Karl-Heinz ^{[13
]}

Langer, Christian ^{[14
]}

Hajek, Roman ^{[15
]}

Goldschmidt, Hartmut ^{[2
,16
]}

Hemminki, Kari ^{[1
,17
]}

Foersti, Asta ^{[1
,17
]}

机构：

[1] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany

[2] Heidelberg Univ, Dept Internal Med 5, Heidelberg, Germany

[3] Univ Arkansas Med Sci, Myeloma Inst, Little Rock, AR 72205 USA

[4] Univ Hosp Brno, Hematol & Oncol, Dept Internal Med, Brno, Czech Republic

[5] Univ Hosp Kralovske Vinohrady, Dept Hematol, Prague, Czech Republic

[6] Acad Sci Czech Republ, Inst Expt Med, Prague, Czech Republic

[7] Charles Univ Prague, Inst Biol & Med Genet, Med Fac 1, Prague, Czech Republic

[8] Charles Univ Prague, Fac Med, Plzen, Czech Republic

[9] Charles Univ Prague, Biomed Ctr Pilsen, Plzen, Czech Republic

[10] Univ Bonn, Inst Human Genet, Bonn, Germany

[11] Univ Basel, Dept Biomed, Basel, Switzerland

[12] Univ Bonn, Dept Genom, Life & Brain Res Ctr, Bonn, Germany

[13] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany

[14] Univ Ulm, Dept Internal Med 3, Ulm, Germany

[15] Univ Hosp Ostrava, Dept Hematooncol, Ostrava, Czech Republic

[16] Natl Ctr Tumor Dis, Heidelberg, Germany

[17] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden

来源：

EUROPEAN JOURNAL OF HAEMATOLOGY | 2017年 / 99卷 / 01期

关键词：

germ line; low-risk genes; myeloma; susceptibility; INHERITED GENETIC SUSCEPTIBILITY; ACUTE LYMPHOBLASTIC-LEUKEMIA; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; FUNCTIONAL VARIATION; WIDE ASSOCIATION; RISK-FACTORS; VARIANTS; LOCI; RECOGNITION;

D O I：

10.1111/ejh.12892

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectivesTo identify germ line variants contributing to the development of monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant precursor for multiple myeloma (MM). MethodsWe conducted the first genomewide association study (GWAS) on MGUS on 243 German cases with a replication on 294 Czech cases. Identified loci were further analyzed in 1508 German MM patients. New MM loci recently reported in a meta-analysis were also tested in the MGUS GWAS. ResultsIn GWAS, we identified 10 loci contributing to development of MGUS at P-value threshold of 10(-5). The Czech cohort gave support for two associations (6q26, rs6933936; 7p21.3 rs10251201). In GWAS, rs974120 (8p23.2) reached genomewide significance (P=2.94x10(-9)), with a nominal significance in MM. The locus of rs974120 shows marks of transcriptional activity in leukemia according to ENCODE data. rs10251201 (7p21.3), rs9318227 (13q22.1), and rs10405859 (19q13.32) were associated with markers related to leukemogenesis and immune and inflammatory responses. Two newly identified candidate loci for MM, rs1948915 (8q24.21) and rs8058578 (16p11.2), were nominally associated with MGUS. ConclusionsThese data allow a cautious first proposal for a germ line architecture of MGUS with links to leukemia and autoimmune conditions, the latter agreeing with a family study showing clustering of MGUS with autoimmune diseases.

引用

页码：70 / 79

页数：10

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