Genome-Wide Association Study Identifies the First Germline Genetic Variant Associated With Erdheim-Chester Disease

被引：5

作者：

Martinez-Lopez, Javier ^{[1
]}

Marquez, Ana ^{[1
]}

Pegoraro, Francesco ^{[2
,3
]}

Ortiz-Fernandez, Lourdes ^{[1
]}

Acosta-Herrera, Marialbert ^{[4
,5
]}

Kerick, Martin ^{[1
]}

Gelain, Elena ^{[6
]}

Diamond, Eli L. ^{[7
]}

Durham, Benjamin H. ^{[7
]}

Abdel-Wahab, Omar ^{[7
]}

Go, Ronald S. ^{[8
]}

Koster, Matthew J. ^{[8
]}

Dagna, Lorenzo ^{[9
,10
]}

Campochiaro, Corrado ^{[9
,10
]}

Collin, Matthew ^{[11
]}

Milne, Paul ^{[11
]}

Estrada-Veras, Juvianee I. ^{[12
]}

O'Brien, Kevin ^{[12
]}

Papo, Matthias ^{[13
,14
]}

Cohen-Aubar, Fleur ^{[13
]}

Amoura, Zahir ^{[13
,14
]}

Haroche, Julien ^{[13
,14
]}

Martin, Javier ^{[1
]}

Vaglio, Augusto ^{[2
,3
]}

机构：

[1] Inst Parasitol & Biomed Lopez Neyra, Consejo Super Invest Cient, Granada, Spain

[2] Univ Florence, Florence, Italy

[3] Meyer Childrens Hosp, Inst Ricovero & Cura Carattere Sci IRCCS, Florence, Italy

[4] Ibs Granada Inst Invest Biosanit, Inst Parasitol & Biomed Lopez Neyra, Consejo Super Invest Cient, Granada, Spain

[5] Ibs Granada Inst Invest Biosanit, Hosp Clin San Cecilio, Granada, Spain

[6] Meyer Childrens Hosp, Inst Ricovero & Cura Carattere Sci IRCCS, Florence, Italy

[7] Mem Sloan Kettering Canc Ctr, New York, NY USA

[8] Mayo Clin, Rochester, MN USA

[9] Ist Sci San Raffaele, Inst Ricovero & Cura Carattere Sci IRCCS, Milan, Italy

[10] Univ Vita Salute San Raffaele, Milan, Italy

[11] Newcastle Univ, Newcastle Upon Tyne, England

[12] NIH, Natl Human Genome Res Inst, Bethesda, MD USA

[13] Sorbonne Univ, AP HP, Serv Med Interne, Paris, France

[14] Hop La Pitie Salpetriere, Ctr Natl Reference Malad Syst Rares & Histiocytose, Ctr immunol & Malad infectieuses, INSERM,UMRS1135, Paris, France

来源：

ARTHRITIS & RHEUMATOLOGY | 2024年 / 76卷 / 01期

关键词：

MUTATIONS; COMPLEX; COMMON;

D O I：

10.1002/art.42673

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. Erdheim-Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome-wide association study.Methods. After quality controls, a cohort of 255 patients with ECD and 7,471 healthy donors was included in this study. Afterward, a logistic regression followed by in silico functional annotation was performed.Results. A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (P = 2.75 x 10(-11); Odds Ratio = 2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease.Conclusion. Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role.

引用

页码：141 / 145

页数：5

共 15 条

[1] The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease [J].

Astle, William J. ;

Elding, Heather ;

Jiang, Tao ;

Allen, Dave ;

Ruklisa, Dace ;

Mann, Alice L. ;

Mead, Daniel ;

Bouman, Heleen ;

Riveros-Mckay, Fernando ;

Kostadima, Myrto A. ;

Lambourne, John J. ;

Sivapalaratnam, Suthesh ;

Downes, Kate ;

Kundu, Kousik ;

Bomba, Lorenzo ;

Berentsen, Kim ;

Bradley, John R. ;

Daugherty, Louise C. ;

Delaneau, Olivier ;

Freson, Kathleen ;

Garner, Stephen F. ;

Grassi, Luigi ;

Guerrero, Jose ;

Haimel, Matthias ;

Janssen-Megens, Eva M. ;

Kaan, Anita ;

Kamat, Mihir ;

Kim, Bowon ;

Mandoli, Amit ;

Marchini, Jonathan ;

Martens, Joost H. A. ;

Meacham, Stuart ;

Megy, Karyn ;

O'Connell, Jared ;

Petersen, Romina ;

Sharifi, Nilofar ;

Sheard, Simon M. ;

Staley, James R. ;

Tuna, Salih ;

van der Ent, Martijn ;

Walter, Klaudia ;

Wang, Shuang-Yin ;

Wheeler, Eleanor ;

Wilder, Steven P. ;

Iotchkova, Valentina ;

Moore, Carmel ;

Sambrook, Jennifer ;

Stunnenberg, Hendrik G. ;

Di Angelantonio, Emanuele ;

Kaptoge, Stephen .

CELL, 2016, 167 (05) :1415-+

[2] High frequency of clonal hematopoiesis in Erdheim-Chester disease [J].

Aubart, Fleur Cohen ;

Roos-Weil, Damien ;

Armand, Marine ;

Marceau-Renaut, Alice ;

Emile, Jean-Francois ;

Duployez, Nicolas ;

Charlotte, Frederic ;

Poulain, Stephanie ;

Lhote, Raphael ;

Helias-Rodzewicz, Zofia ;

Della-Valle, Veronique ;

Bernard, Olivier ;

Maloum, Karim ;

Nguyen-Khac, Florence ;

Donadieu, Jean ;

Amoura, Zahir ;

Abdel-Wahab, Omar ;

Haroche, Julien .

BLOOD, 2021, 137 (04) :485-492

[3] Copper is required for oncogenic BRAF signalling and tumorigenesis [J].

Brady, Donita C. ;

Crowe, Matthew S. ;

Turski, Michelle L. ;

Hobbs, G. Aaron ;

Yao, Xiaojie ;

Chaikuad, Apirat ;

Knapp, Stefan ;

Xiao, Kunhong ;

Campbell, Sharon L. ;

Thiele, Dennis J. ;

Counter, Christopher M. .

NATURE, 2014, 509 (7501) :492-+

[4] Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease [J].

Emile, Jean-Francois ;

Diamond, Eli L. ;

Helias-Rodzewicz, Zofia ;

Cohen-Aubart, Fleur ;

Charlotte, Frederic ;

Hyman, David M. ;

Kim, Eunhee ;

Rampal, Raajit ;

Patel, Minal ;

Ganzel, Chezi ;

Aumann, Shlomzion ;

Faucher, Gladwys ;

Le Gall, Catherine ;

Leroy, Karen ;

Colombat, Magali ;

Kahn, Jean-Emmanuel ;

Trad, Salim ;

Nizard, Philippe ;

Donadieu, Jean ;

Taly, Valerie ;

Amoura, Zahir ;

Abdel-Wahab, Omar ;

Haroche, Julien .

BLOOD, 2014, 124 (19) :3016-3019

[5] Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial [J].

Gianfreda, Davide ;

Nicastro, Maria ;

Galetti, Maricla ;

Alberici, Federico ;

Corradi, Domenico ;

Becchi, Gabriella ;

Baldari, Giorgio ;

De Filippo, Massimo ;

Ferretti, Stefania ;

Moroni, Gabriella ;

Foti, Rosario ;

Di Gangi, Marcella ;

Jeannin, Guido ;

Saffroy, Raphael ;

Emile, Jean-Francois ;

Buzio, Carlo ;

Vaglio, Augusto .

BLOOD, 2015, 126 (10) :1163-1171

[6] Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era [J].

Goyal, Gaurav ;

Heaney, Mark L. ;

Collin, Matthew ;

Cohen-Aubart, Fleur ;

Vaglio, Augusto ;

Durham, Benjamin H. ;

Hershkovitz-Rokah, Oshrat ;

Girschikofsky, Michael ;

Jacobsen, Eric D. ;

Toyama, Kazuhiro ;

Goodman, Aaron M. ;

Hendrie, Paul ;

Cao, Xin-xin ;

Estrada-Veras, Juvianee I. ;

Shpilberg, Ofer ;

Abdo, Andre ;

Kurokawa, Mineo ;

Dagna, Lorenzo ;

McClain, Kenneth L. ;

Mazor, Roei D. ;

Picarsic, Jennifer ;

Janku, Filip ;

Go, Ronald S. ;

Haroche, Julien ;

Diamond, Eli L. .

BLOOD, 2020, 135 (22) :1929-1945

[7] Erdheim-Chester disease [J].

Haroche, Julien ;

Cohen-Aubart, Fleur ;

Amoura, Zahir .

BLOOD, 2020, 135 (16) :1311-1318

[8] Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases [J].

Kanai, Masahiro ;

Akiyama, Masato ;

Takahashi, Atsushi ;

Matoba, Nana ;

Momozawa, Yukihide ;

Ikeda, Masashi ;

Iwata, Nakao ;

Ikegawa, Shiro ;

Hirata, Makoto ;

Matsuda, Koichi ;

Kubo, Michiaki ;

Okada, Yukinori ;

Kamatani, Yoichiro .

NATURE GENETICS, 2018, 50 (03) :390-+

[9] Common and rare variant associations with clonal haematopoiesis phenotypes [J].

Kessler, Michael D. ;

Damask, Amy ;

O'Keeffe, Sean ;

Banerjee, Nilanjana ;

Li, Dadong ;

Watanabe, Kyoko ;

Marketta, Anthony ;

Van Meter, Michael ;

Semrau, Stefan ;

Horowitz, Julie ;

Tang, Jing ;

Kosmicki, Jack A. ;

Rajagopal, Veera M. ;

Zou, Yuxin ;

Houvras, Yariv ;

Ghosh, Arkopravo ;

Gillies, Christopher ;

Mbatchou, Joelle ;

White, Ryan R. ;

Verweij, Niek ;

Bovijn, Jonas ;

Parikshak, Neelroop N. ;

LeBlanc, Michelle G. ;

Jones, Marcus ;

Glass, David J. ;

Lotta, Luca A. ;

Cantor, Michael N. ;

Atwal, Gurinder S. ;

Locke, Adam E. ;

Ferreira, Manuel A. R. ;

Deering, Raquel ;

Paulding, Charles ;

Shuldiner, Alan R. ;

Thurston, Gavin ;

Ferrando, Adolfo A. ;

Salerno, Will ;

Reid, Jeffrey G. ;

Overton, John D. ;

Marchini, Jonathan ;

Kang, Hyun M. ;

Baras, Aris ;

Abecasis, Goncalo R. ;

Jorgenson, Eric .

NATURE, 2022, 612 (7939) :301-+

[10] Somatic SETBP1 mutations in myeloid malignancies [J].

Makishima, Hideki ;

Yoshida, Kenichi ;

Nhu Nguyen ;

Przychodzen, Bartlomiej ;

Sanada, Masashi ;

Okuno, Yusuke ;

Ng, Kwok Peng ;

Gudmundsson, Kristbjorn O. ;

Vishwakarma, Bandana A. ;

Jerez, Andres ;

Gomez-Segui, Ines ;

Takahashi, Mariko ;

Shiraishi, Yuichi ;

Nagata, Yasunobu ;

Guinta, Kathryn ;

Mori, Hiraku ;

Sekeres, Mikkael A. ;

Chiba, Kenichi ;

Tanaka, Hiroko ;

Muramatsu, Hideki ;

Sakaguchi, Hirotoshi ;

Paquette, Ronald L. ;

McDevitt, Michael A. ;

Kojima, Seiji ;

Saunthararajah, Yogen ;

Miyano, Satoru ;

Shih, Lee-Yung ;

Du, Yang ;

Ogawa, Seishi ;

Maciejewski, Jaroslaw P. .

NATURE GENETICS, 2013, 45 (08) :942-U298

← 1 2 →