A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis

被引：74

作者：

David Carmona, F. ^{[1
,2
,3
]}

Vaglio, Augusto ^{[4
]}

Mackie, Sarah L. ^{[5
,6
]}

Hernandez-Rodriguez, Jose ^{[7
]}

Monach, Paul A. ^{[8
]}

Castaneda, Santos ^{[9
]}

Solans, Roser ^{[10
]}

Morado, Inmaculada C. ^{[11
]}

Narvaez, Javier ^{[12
]}

Ramentol-Sintas, Marc ^{[10
]}

Pease, Colin T. ^{[5
,6
]}

Dasgupta, Bhaskar ^{[13
]}

Watts, Richard ^{[14
]}

Khalidi, Nader ^{[15
]}

Langford, Carol A. ^{[16
]}

Ytterberg, Steven ^{[17
]}

Boiardi, Luigi ^{[18
]}

Beretta, Lorenzo ^{[19
]}

Govoni, Marcello ^{[20
]}

Emmi, Giacomo ^{[21
]}

Bonatti, Francesco ^{[22
]}

Cimmino, Marco A. ^{[23
,24
]}

Witte, Torsten ^{[25
]}

Neumann, Thomas ^{[26
]}

Holle, Julia ^{[27
,28
]}

Schoenau, Verena ^{[29
]}

Sailler, Laurent ^{[30
]}

Papo, Thomas ^{[31
]}

Haroche, Julien ^{[32
,33
]}

Mahr, Alfred ^{[34
]}

Mouthon, Luc ^{[35
]}

Molberg, Oyvind ^{[36
]}

Diamantopoulos, Andreas P. ^{[37
]}

Voskuyl, Alexandre ^{[38
]}

Brouwer, Elisabeth ^{[39
]}

Daikeler, Thomas ^{[40
]}

Berger, Christoph T. ^{[41
,42
]}

Molloy, Eamonn S. ^{[43
]}

O'Neill, Lorraine ^{[43
]}

Blockmans, Daniel ^{[44
]}

Lie, Benedicte A. ^{[45
,46
]}

Mclaren, Paul ^{[47
]}

Vyse, Timothy J. ^{[48
,49
,50
]}

Wijmenga, Cisca ^{[51
]}

Allanore, Yannick ^{[52
]}

Koeleman, Bobby P. C. ^{[53
]}

Barrett, Jennifer H. ^{[5
,6
]}

Cid, Maria C. ^{[7
]}

Salvarani, Carlo ^{[18
]}

Merkel, Peter A. ^{[54
]}

机构：

[1] PTS Granada, CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain

[2] Univ Granada, Dept Genet, Granada 18016, Spain

[3] Univ Granada, Inst Biotecnol, Granada 18016, Spain

[4] Univ Hosp Parma, Unit Nephrol, I-43126 Parma, Italy

[5] Univ Leeds, Sch Med, Leeds LS7 4SA, W Yorkshire, England

[6] Leeds Teaching Hosp NHS Trust, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds LS7 4SA, W Yorkshire, England

[7] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Vasculitis Res Unit,Dept Autoimmune Dis, E-08036 Barcelona, Spain

[8] Boston Univ, Sect Rheumatol, Boston, MA 02118 USA

[9] Hosp Princesa, IIS IP, Dept Rheumatol, Madrid 28006, Spain

[10] Autonomous Univ Barcelona, Hosp Vall dHebron, Dept Internal Med, Autoimmune Syst Dis Unit, E-08035 Barcelona, Spain

[11] Hosp Clin San Carlos, Dept Rheumatol, Madrid 28040, Spain

[12] Hosp Univ Bellvitge IDIBELL, Dept Rheumatol, Barcelona 08907, Spain

[13] Southend Univ Hosp NHS Fdn Trust, Dept Rheumatol, Westcliff On Sea SS0 0RY, England

[14] Ipswich Hosp NHS Trust, Dept Rheumatol, Ipswich IP4 5PD, Suffolk, England

[15] McMaster Univ, Div Rheumatol, Hamilton, ON L8N 1Y2, Canada

[16] Cleveland Clin, Div Rheumatol, Cleveland, OH 44195 USA

[17] Mayo Clin, Div Rheumatol, Rochester, MN 55905 USA

[18] Azienda Osped Arcispedale Santa Maria Nuova, Ist Ricovero & Cura Carattere Sci, Dept Internal Med, Rheumatol Unit, I-42123 Reggio Emilia, Italy

[19] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Referral Ctr System Autoimmune Dis, I-20122 Milan, Italy

[20] Univ Ferrara, Azienda Osped Univ S Anna, Dept Rheumatol, I-44121 Ferrara, Italy

[21] Univ Florence, Dept Expt & Clin Med, I-50134 Florence, Italy

[22] Univ Parma, Med Genet Unit, Dept Clin & Expt Med, I-43124 Parma, Italy

[23] Univ Genoa, Dept Internal Med, Res Lab, I-16132 Genoa, Italy

[24] Univ Genoa, Dept Internal Med, Acad Div Clin Rheumatol, I-16132 Genoa, Italy

[25] Hannover Med Sch, D-30625 Hannover, Germany

[26] Univ Hosp Jena, Innere Med Klin 3, D-07743 Jena, Germany

[27] Klinikum Bad Bramstedt, Vasculitis Clin, D-24576 Bad Bramstedt, Germany

[28] Univ Hosp Schleswig Holstein, D-24576 Bad Bramstedt, Germany

[29] Univ Klinikum Erlangen, Dept Rheumatol & Immunol, D-91054 Erlangen, Germany

[30] Univ Toulouse, CHU Toulouse, INSERM, Serv Med Interne,Hop Purpan,UMR 1027, F-31059 Toulouse, France

[31] Univ Paris Diderot, Hop Bichat, Serv Med Interne, F-75018 Paris, France

[32] Hop La Pitie Salpetriere, AP HP, Dept Internal Med, F-75013 Paris, France

[33] Hop La Pitie Salpetriere, AP HP, French Reference Ctr Rare Autoimmune & Syst Dis, F-75013 Paris, France

[34] Univ Paris Diderot, Host St Louis, ECSTRA Team,UMR 1153, Sorbonne Paris Cite,Res Ctr,Dept Internal Med,Epi, F-75010 Paris, France

[35] Univ Paris 05, Cochin Hosp, AP HP, Natl Referral Ctr Rare Autoimmune & Syst Dis,Dept, F-75014 Paris, France

[36] Oslo Univ Hosp, Dept Rheumatol, N-0424 Oslo, Norway

[37] Hosp Southern Norway Trust, Dept Rheumatol, N-4604 Kristiansand, Norway

[38] Vrije Univ Amsterdam, Med Ctr, Amsterdam Rheumatol & Immunol Ctr, NL-1007 MB Amsterdam, Netherlands

[39] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, NL-9713 GZ Groningen, Netherlands

[40] Univ Hosp, Rheumatol Dept Internal Med, CH-4056 Basel, Switzerland

[41] Univ Hosp, Translat Immunol & Med Outpatient Clin, Dept Biomed, CH-4056 Basel, Switzerland

[42] Univ Hosp, Translat Immunol & Med Outpatient Clin, Dept Internal Med, CH-4056 Basel, Switzerland

[43] St Vincents Univ Hosp, Dublin Acad Med Ctr, Ctr Arthrit & Rheumat Dis, Dept Rheumatol, Dublin 4, Ireland

[44] Univ Hosp Gasthuisberg, Dept Gen Internal Med, B-3000 Leuven, Belgium

[45] Univ Oslo, Dept Med Genet, N-0450 Oslo, Norway

[46] Oslo Univ Hosp, N-0450 Oslo, Norway

[47] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[48] Kings Coll London, Div Genet, London SE1 9RT, England

[49] Kings Coll London, Div Mol Med, London SE1 9RT, England

[50] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London SE1 9RT, England

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2017年 / 100卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

FUNCTIONAL VARIATION; DISEASE; PATHOGENESIS; VARIANTS; INSIGHTS; HYPOXIA; GENES; TOOL;

D O I：

10.1016/j.ajhg.2016.11.013

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than SO years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 x 10(-54), per-allele OR = 1.79; and rs9275592, p = 1.14 x 10(-4), OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 x 10(-10), OR = 1.28; and rs128738, p = 4.60 x 10(-9), OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.

引用

页码：64 / 74

页数：11

共 50 条

[1] Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study
Borrego-Yaniz, Gonzalo
Ortiz-Fernandez, Lourdes
Madrid-Paredes, Adela
Kerick, Martin
Hernandez-Rodriguez, Jose
Mackie, Sarah L.
Vaglio, Augusto
Castaneda, Santos
Solans, Roser
Mestre-Torres, Jaume
Khalidi, Nader
Langford, Carol A.
Ytterberg, Steven
Beretta, Lorenzo
Govoni, Marcello
Emmi, Giacomo
Cimmino, Marco A.
Witte, Torsten
Neumann, Thomas
Holle, Julia
Schoenau, Verena
Pugnet, Gregory
Papo, Thomas
Haroche, Julien
Mahr, Alfred
Mouthon, Luc
Molberg, Oyvind
Diamantopoulos, Andreas P.
Voskuyl, Alexandre
Daikeler, Thomas
Berger, Christoph T.
Molloy, Eamonn S.
Blockmans, Daniel
van Sleen, Yannick
Iles, Mark
Sorensen, Louise
Luqmani, Raashid
Reynolds, Gary
Bukhari, Marwan
Bhagat, Shweta
Ortego-Centeno, Norberto
Brouwer, Elisabeth
Lamprecht, Peter
Klapa, Sebastian
Salvarani, Carlo
Merkel, Peter A.
Cid, Maria C.
Gonzalez-Gay, Miguel A.
Morgan, Ann W.
Martin, Javier
LANCET RHEUMATOLOGY, 2024, 6 (06) : e374 - e383
[2] Genome-wide association study identifies three loci associated with melanoma risk
Bishop, D. Timothy
Demenais, Florence
Iles, Mark M.
Harland, Mark
Taylor, John C.
Corda, Eve
Randerson-Moor, Juliette
Aitken, Joanne F.
Avril, Marie-Francoise
Azizi, Esther
Bakker, Bert
Bianchi-Scarra, Giovanna
Bressac-de Paillerets, Brigitte
Calista, Donato
Cannon-Albright, Lisa A.
Chin-A-Woeng, Thomas
Debniak, Tadeusz
Galore-Haskel, Gilli
Ghiorzo, Paola
Gut, Ivo
Hansson, Johan
Hocevar, Marko
Hoiom, Veronica
Hopper, John L.
Ingvar, Christian
Kanetsky, Peter A.
Kefford, Richard F.
Landi, Maria Teresa
Lang, Julie
Lubinski, Jan
Mackie, Rona
Malvehy, Josep
Mann, Graham J.
Martin, Nicholas G.
Montgomery, Grant W.
van Nieuwpoort, Frans A.
Novakovic, Srdjan
Olsson, Hakan
Puig, Susana
Weiss, Marjan
van Workum, Wilbert
Zelenika, Diana
Brown, Kevin M.
Goldstein, Alisa M.
Gillanders, Elizabeth M.
Boland, Anne
Galan, Pilar
Elder, David E.
Gruis, Nelleke A.
Hayward, Nicholas K.
NATURE GENETICS, 2009, 41 (08) : 920 - U85
[3] Genome-wide association study identifies 30 loci associated with bipolar disorder
Stahl, Eli A.
Breen, Gerome
Forstner, Andreas J.
McQuillin, Andrew
Ripke, Stephan
Trubetskoy, Vassily
Mattheisen, Manuel
Wang, Yunpeng
Coleman, Jonathan R. I.
Gaspar, Helena A.
de Leeuw, Christiaan A.
Steinberg, Stacy
Pavlides, Jennifer M. Whitehead
Trzaskowski, Maciej
Byrne, Enda M.
Pers, Tune H.
Holmans, Peter A.
Richards, Alexander L.
Abbott, Liam
Agerbo, Esben
Akil, Huda
Albani, Diego
Alliey-Rodriguez, Ney
Als, Thomas D.
Anjorin, Adebayo
Antilla, Verneri
Awasthi, Swapnil
Badner, Judith A.
Baekvad-Hansen, Marie
Barchas, Jack D.
Bass, Nicholas
Bauer, Michael
Belliveau, Richard
Bergen, Sarah E.
Pedersen, Carsten Bocker
Boen, Erlend
Boks, Marco P.
Boocock, James
Budde, Monika
Bunney, William
Burmeister, Margit
Bybjerg-Grauholm, Jonas
Byerley, William
Casas, Miquel
Cerrato, Felecia
Cervantes, Pablo
Chambert, Kimberly
Charney, Alexander W.
Chen, Danfeng
Churchhouse, Claire
NATURE GENETICS, 2019, 51 (05) : 793 - +
[4] Genome-wide association study identifies multiple risk loci for renal cell carcinoma
Scelo, Ghislaine
Purdue, Mark P.
Brown, Kevin M.
Johansson, Mattias
Wang, Zhaoming
Eckel-Passow, Jeanette E.
Ye, Yuanqing
Hofmann, Jonathan N.
Choi, Jiyeon
Foll, Matthieu
Gaborieau, Valerie
Machiela, Mitchell J.
Colli, Leandro M.
Li, Peng
Sampson, Joshua N.
Abedi-Ardekani, Behnoush
Besse, Celine
Blanche, Helene
Boland, Anne
Burdette, Laurie
Chabrier, Amelie
Durand, Geoffroy
Le Calvez-Kelm, Florence
Prokhortchouk, Egor
Robinot, Nivonirina
Skryabin, Konstantin G.
Wozniak, Magdalena B.
Yeager, Meredith
Basta-Jovanovic, Gordana
Dzamic, Zoran
Foretova, Lenka
Holcatova, Ivana
Janout, Vladimir
Mates, Dana
Mukeriya, Anush
Rascu, Stefan
Zaridze, David
Bencko, Vladimir
Cybulski, Cezary
Fabianova, Eleonora
Jinga, Viorel
Lissowska, Jolanta
Lubinski, Jan
Navratilova, Marie
Rudnai, Peter
Szeszenia-Dabrowska, Neonila
Benhamou, Simone
Cancel-Tassin, Geraldine
Cussenot, Olivier
Baglietto, Laura
NATURE COMMUNICATIONS, 2017, 8
[5] Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes
Miller, F. W.
Chen, W.
O'Hanlon, T. P.
Cooper, R. G.
Vencovsky, J.
Rider, L. G.
Danko, K.
Wedderburn, L. R.
Lundberg, I. E.
Pachman, L. M.
Reed, A. M.
Ytterberg, S. R.
Padyukov, L.
Selva-O'Callaghan, A.
Radstake, T. R.
Isenberg, D. A.
Chinoy, H.
Ollier, W. E. R.
Scheet, P.
Peng, B.
Lee, A.
Byun, J.
Lamb, J. A.
Gregersen, P. K.
Amos, C. I.
GENES AND IMMUNITY, 2015, 16 (07) : 470 - 480
[6] A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury
Singer, Jonathan B.
Lewitzky, Steve
Leroy, Elisabeth
Yang, Fan
Zhao, Xiaojun
Klickstein, Lloyd
Wright, Timothy M.
Meyer, Joanne
Paulding, Charles A.
NATURE GENETICS, 2010, 42 (08) : 711 - U94
[7] Genome-wide association study identifies five loci associated with lung function
Repapi, Emmanouela
Sayers, Ian
Wain, Louise V.
Burton, Paul R.
Johnson, Toby
Obeidat, Ma'en
Zhao, Jing Hua
Ramasamy, Adaikalavan
Zhai, Guangju
Vitart, Veronique
Huffman, Jennifer E.
Igl, Wilmar
Albrecht, Eva
Deloukas, Panos
Henderson, John
Granell, Raquel
McArdle, Wendy L.
Rudnicka, Alicja R.
Barroso, Ines
Loos, Ruth J. F.
Wareham, Nicholas J.
Mustelin, Linda
Rantanen, Taina
Surakka, Ida
Imboden, Medea
Wichmann, H. Erich
Grkovic, Ivica
Jankovic, Stipan
Zgaga, Lina
Hartikainen, Anna-Liisa
Peltonen, Leena
Gyllensten, Ulf
Johansson, Asa
Zaboli, Ghazal
Campbell, Harry
Wild, Sarah H.
Wilson, James F.
Glaeser, Sven
Homuth, Georg
Voelzke, Henry
Mangino, Massimo
Soranzo, Nicole
Spector, Tim D.
Polasek, Ozren
Rudan, Igor
Wright, Alan F.
Heliovaara, Markku
Ripatti, Samuli
Pouta, Anneli
Naluai, Asa Torinsson
NATURE GENETICS, 2010, 42 (01) : 36 - U51
[8] A genome-wide association study identifies 41 loci associated with eicosanoid levels
Rhee, Eugene P.
Surapaneni, Aditya L.
Schlosser, Pascal
Alotaibi, Mona
Yang, Yueh-ning
Coresh, Josef
Jain, Mohit
Cheng, Susan
Yu, Bing
Grams, Morgan E.
COMMUNICATIONS BIOLOGY, 2023, 6 (01)
[9] A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility
Peckham-Gregory, Erin C.
Chakraborty, Rikhia
Scheurer, Michael E.
Belmont, John W.
Abhyankar, Harshal
Sengal, Amel G.
Scull, Brooks P.
Eckstein, Olive
Zinn, Daniel J.
Mayer, Louisa
Shih, Albert
Merad, Miriam
Parsons, D. Williams
McClain, Kenneth L.
Lupo, Philip J.
Allen, Carl E.
BLOOD, 2017, 130 (20) : 2229 - 2232
[10] A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma
Landi, Maria Teresa
Chatterjee, Nilanjan
Yu, Kai
Goldin, Lynn R.
Goldstein, Alisa M.
Rotunno, Melissa
Mirabello, Lisa
Jacobs, Kevin
Wheeler, William
Yeager, Meredith
Bergen, Andrew W.
Li, Qizhai
Consonni, Dario
Pesatori, Angela C.
Wacholder, Sholom
Thun, Michael
Diver, Ryan
Oken, Martin
Virtamo, Jarmo
Albanes, Demetrius
Wang, Zhaoming
Burdette, Laurie
Doheny, Kimberly F.
Pugh, Elizabeth W.
Laurie, Cathy
Brennan, Paul
Hung, Rayjean
Gaborieau, Valerie
McKay, James D.
Lathrop, Mark
McLaughlin, John
Wang, Ying
Tsao, Ming-Sound
Spitz, Margaret R.
Wang, Yufei
Krokan, Hans
Vatten, Lars
Skorpen, Frank
Arnesen, Egil
Benhamou, Simone
Bouchard, Christine
Metsapalu, Andres
Vooder, Tonu
Nelis, Mari
Vaelk, Kristian
Field, John K.
Chen, Chu
Goodman, Gary
Sulem, Patrick
Thorleifsson, Gudmar
AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (05) : 679 - 691

← 1 2 3 4 5 →