Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis

被引：172

作者：

Hirschfield, Gideon M. ^{[1
,2
]}

Liu, Xiangdong ^{[1
,3
,4
]}

Han, Younghun ^{[5
]}

Gorlov, Ivan P. ^{[5
]}

Lu, Yan ^{[1
,3
,4
]}

Xu, Chun ^{[1
,3
,4
]}

Lu, Yue ^{[5
]}

Chen, Wei ^{[5
]}

Juran, Brian D. ^{[6
]}

Coltescu, Catalina ^{[2
]}

Mason, Andrew L. ^{[7
]}

Milkiewicz, Piotr ^{[8
]}

Myers, Robert P. ^{[9
]}

Odin, Joseph A. ^{[10
]}

Luketic, Velimir A. ^{[11
]}

Speiciene, Danute ^{[12
]}

Vincent, Catherine ^{[13
]}

Levy, Cynthia ^{[14
]}

Gregersen, Peter K. ^{[15
]}

Zhang, Jinyi ^{[1
,3
,4
]}

Heathcote, E. Jenny ^{[1
,2
]}

Lazaridis, Konstantinos N. ^{[6
]}

Amos, Christopher I. ^{[5
]}

Siminovitch, Katherine A. ^{[1
,3
,4
,16
,17
]}

机构：

[1] Univ Toronto, Dept Med, Toronto, ON, Canada

[2] Toronto Western Hosp, Ctr Liver, Toronto, ON M5T 2S8, Canada

[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[4] Toronto Gen Res Inst, Toronto, ON, Canada

[5] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[6] Mayo Clin, Ctr Basic Res Digest Dis, Div Gastroenterol & Hepatol, Coll Med, Rochester, MN USA

[7] Univ Alberta, Dept Med, Edmonton, AB, Canada

[8] Pomeranian Med Sch, Liver Unit, Szczecin, Poland

[9] Univ Calgary, Liver Unit, Calgary, AB, Canada

[10] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA

[11] Virginia Commonwealth Univ, Dept Gastroenterol, Richmond, VA USA

[12] Vilnius State Univ, Ctr Gastroenterol & Dietet, Vilnius, Lithuania

[13] Univ Montreal, St Luc Hosp, Ctr Hosp, Montreal, PQ, Canada

[14] Univ Florida, Dept Med, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA

[15] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA

[16] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[17] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

来源：

NATURE GENETICS | 2010年 / 42卷 / 08期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; STRONG RISK-FACTOR; RHEUMATOID-ARTHRITIS; POLYMORPHISM; DISEASE; LUPUS; LOCI;

D O I：

10.1038/ng.631

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 x 10(-4)) identified in a previous genome-wide association study. Combined analysis of the genome-wide association and replication datasets identified IRF5-TNPO3 (combined P = 8.66 x 10(-13)), 17q12-21 (combined P = 3.50 x 10(-13)) and MMEL1 (combined P = 3.15 x 10(-8)) as new primary biliary cirrhosis susceptibility loci. Fine-mapping studies showed that a single variant accounts for the IRF5-TNPO3 association. As these loci are implicated in other autoimmune conditions, these findings confirm genetic overlap among such diseases.

引用

页码：655 / 657

页数：3

共 10 条

[1] Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis
Gideon M Hirschfield
Xiangdong Liu
Younghun Han
Ivan P Gorlov
Yan Lu
Chun Xu
Yue Lu
Wei Chen
Brian D Juran
Catalina Coltescu
Andrew L Mason
Piotr Milkiewicz
Robert P Myers
Joseph A Odin
Velimir A Luketic
Danute Speiciene
Catherine Vincent
Cynthia Levy
Peter K Gregersen
Jinyi Zhang
E Jenny Heathcote
Konstantinos N Lazaridis
Christopher I Amos
Katherine A Siminovitch
Nature Genetics, 2010, 42 : 655 - 657
[2] Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort
Tanaka, A.
Invernizzi, P.
Ohira, H.
Kikuchi, K.
Nezu, S.
Kosoy, R.
Seldin, M. F.
Gershwin, M. E.
Takikawa, H.
TISSUE ANTIGENS, 2011, 78 (01): : 65 - 68
[3] REPLICATED ASSOCIATION OF 17Q12-21 WITH SUSCEPTIBILITY OF PRIMARY BILIARY CIRRHOSIS IN A JAPANESE COHORT
Tanaka, A.
Invernizzi, P.
Ohira, H.
Kikuchi, K.
Nezu, S.
Shibuya, A.
Seldin, M. F.
Gershwin, M. E.
Takikawa, H.
JOURNAL OF HEPATOLOGY, 2011, 54 : S518 - S518
[4] Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood
Hallmark, Brian
Wegienka, Ganesa
Havstad, Suzanne
Billheimer, Dean
Ownby, Dennis
Mendonca, Eneida A.
Gress, Lisa
Stern, Debra A.
Myers, Jocelyn Biagini
Hershey, Gurjit K. Khurana
Hoepner, Lori
Miller, Rachel L.
Lemanske, Robert F.
Jackson, Daniel J.
Gold, Diane R.
O'Connor, George T.
Nicolae, Dan L.
Gern, James E.
Ober, Carole
Wright, Anne L.
Martinez, Fernando D.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2021, 203 (07) : 864 - 870
[5] Functional variants of 17q12-21 are associated with allergic asthma but not allergic rhinitis
Andiappan, Anand Kumar
Sio, Yang Yie
Lee, Bernett
Suri, Bani Kaur
Matta, Sri Anusha
Lum, Josephine
Foo, Shihui
Koh, Geraldine
Liu, Jianjun
Zolezzi, Francesca
Poidinger, Michael
Wang, De Yun
Rotzschke, Olaf
Chew, Fook Tim
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2016, 137 (03) : 758 - +
[6] Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis
Yuki Hitomi
Kaname Kojima
Minae Kawashima
Yosuke Kawai
Nao Nishida
Yoshihiro Aiba
Michio Yasunami
Masao Nagasaki
Minoru Nakamura
Katsushi Tokunaga
Scientific Reports, 7
[7] Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis
Hitomi, Yuki
Kojima, Kaname
Kawashima, Minae
Kawai, Yosuke
Nishida, Nao
Aiba, Yoshihiro
Yasunami, Michio
Nagasaki, Masao
Nakamura, Minoru
Tokunaga, Katsushi
SCIENTIFIC REPORTS, 2017, 7
[8] 17q12-21 Variants are associated with asthma and interact with active smoking in an adult population from the United Kingdom
Marinho, Susana
Custovic, Adnan
Marsden, Paul
Smith, Jacky A.
Simpson, Angela
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 2012, 108 (06) : 402 - +
[9] 17q12-21 variants interact with smoke exposure as a risk factor for pediatric asthma but are equally associated with early-onset versus late-onset asthma in North Americans of European ancestry
Flory, James H.
Sleiman, Patrick M.
Christie, Jason D.
Annaiah, Kiran
Bradfield, Jonathan
Kim, Cecilia E.
Glessner, Joseph
Imielinski, Marcin
Li, Hongzhe
Frackelton, Edward C.
Hou Cuiping
Otieno, George
Thomas, Kelly
Smith, Ryan
Glaberson, Wendy
Garris, Maria
Chiavacci, Rosetta
Allen, Julian
Spergel, Jonathan
Grundmeier, Robert
Grunstein, Michael
Magnusson, Michael
Grant, Struan F. A.
Bonnelykke, Klaus
Bisgaard, Hans
Hakonarson, Hakon
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 124 (03) : 605 - 607
[10] Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21
Ayabe, T.
Fukami, M.
Ogata, T.
Kawamura, T.
Urakami, T.
Kikuchi, N.
Yokota, I.
Ihara, K.
Takemoto, K.
Mukai, T.
Nishii, A.
Kikuchi, T.
Mori, T.
Shimura, N.
Sasaki, G.
Kizu, R.
Takubo, N.
Soneda, S.
Fujisawa, T.
Takaya, R.
Kizaki, Z.
Kanzaki, S.
Hanaki, K.
Matsuura, N.
Kasahara, Y.
Kosaka, K.
Takahashi, T.
Minamitani, K.
Matsuo, S.
Mochizuki, H.
Kobayashi, K.
Koike, A.
Horikawa, R.
Teno, S.
Tsubouchi, K.
Mochizuki, T.
Igarashi, Y.
Amemiya, S.
Sugihara, S.
DIABETIC MEDICINE, 2016, 33 (12) : 1717 - 1722

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