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 5 条

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Tanaka, A.
Invernizzi, P.
Ohira, H.
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Seldin, M. F.
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Takikawa, H.
TISSUE ANTIGENS, 2011, 78 (01): : 65 - 68
[2] 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
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Rotzschke, Olaf
Chew, Fook Tim
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2016, 137 (03) : 758 - +
[3] Identification of the functional variant driving ORMDL3 and GSDMB expression in human chromosome 17q12-21 in primary biliary cholangitis
Hitomi, Yuki
Kojima, Kaname
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Kawai, Yosuke
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SCIENTIFIC REPORTS, 2017, 7
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Marinho, Susana
Custovic, Adnan
Marsden, Paul
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Simpson, Angela
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 2012, 108 (06) : 402 - +
[5] Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21
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DIABETIC MEDICINE, 2016, 33 (12) : 1717 - 1722

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