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

doi:10.1038/ng.631

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 ZhangE. Jenny Heathcote, Konstantinos N. Lazaridis, Christopher I. Amos, Katherine A. Siminovitch

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

169 Scopus citations

Abstract

We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 × 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 × 10^-13), 17q12-21 (combined P = 3.50 × 10^-13) and MMEL1 (combined P = 3.15 × 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.

Original language	English (US)
Pages (from-to)	655-657
Number of pages	3
Journal	Nature Genetics
Volume	42
Issue number	8
DOIs	https://doi.org/10.1038/ng.631
State	Published - Aug 2010

ASJC Scopus subject areas

Genetics

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Hirschfield, G. M., Liu, X., Han, Y., Gorlov, I. P., Lu, Y., Xu, C., Lu, Y., Chen, W., Juran, B. D., Coltescu, C., Mason, A. L., Milkiewicz, P., Myers, R. P., Odin, J. A., Luketic, V. A., Speiciene, D., Vincent, C., Levy, C., Gregersen, P. K., ... Siminovitch, K. A. (2010). Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nature Genetics, 42(8), 655-657. https://doi.org/10.1038/ng.631

Hirschfield, GM, Liu, X, Han, Y, Gorlov, IP, Lu, Y, Xu, C, Lu, Y, Chen, W, Juran, BD, Coltescu, C, Mason, AL, Milkiewicz, P, Myers, RP, Odin, JA, Luketic, VA, Speiciene, D, Vincent, C, Levy, C, Gregersen, PK, Zhang, J, Heathcote, EJ, Lazaridis, KN, Amos, CI & Siminovitch, KA 2010, 'Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis', Nature Genetics, vol. 42, no. 8, pp. 655-657. https://doi.org/10.1038/ng.631

@article{768b0251963d4073b358f353b6627ade,

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

abstract = "We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 × 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 × 10-13), 17q12-21 (combined P = 3.50 × 10-13) and MMEL1 (combined P = 3.15 × 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.",

author = "Hirschfield, {Gideon M.} and Xiangdong Liu and Younghun Han and Gorlov, {Ivan P.} and Yan Lu and Chun Xu and Yue Lu and Wei Chen and Juran, {Brian D.} and Catalina Coltescu and Mason, {Andrew L.} and Piotr Milkiewicz and Myers, {Robert P.} and Odin, {Joseph A.} and Luketic, {Velimir A.} and Danute Speiciene and Catherine Vincent and Cynthia Levy and Gregersen, {Peter K.} and Jinyi Zhang and Heathcote, {E. Jenny} and Lazaridis, {Konstantinos N.} and Amos, {Christopher I.} and Siminovitch, {Katherine A.}",

note = "Funding Information: This research was supported by grants from the Canadian Institutes for Health Research (MOP 74621), the Ontario Research Fund (RE01-061), the Canadian Primary Biliary Cirrhosis Society, the Canadian Foundation for Innovation, the Ben and Hilda Katz Charitable Foundation, the US National Institutes of Health (K23 DK68290, RO3 DK78527 and RO1 DK80670), the American Gastroenterological Association and the A.J. and Sigismunda Palumbo Charitable Trust. K.A.S. is a recipient of a Canada Research Chair award. We thank all the study subjects and supporting physicians as well as the technical staff of the University Health Network Analytical Genetics Technology Centre for their assistance in this research.",

year = "2010",

month = aug,

doi = "10.1038/ng.631",

language = "English (US)",

volume = "42",

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T1 - Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis

AU - Hirschfield, Gideon M.

AU - Liu, Xiangdong

AU - Han, Younghun

AU - Gorlov, Ivan P.

AU - Lu, Yan

AU - Xu, Chun

AU - Lu, Yue

AU - Chen, Wei

AU - Juran, Brian D.

AU - Coltescu, Catalina

AU - Mason, Andrew L.

AU - Milkiewicz, Piotr

AU - Myers, Robert P.

AU - Odin, Joseph A.

AU - Luketic, Velimir A.

AU - Speiciene, Danute

AU - Vincent, Catherine

AU - Levy, Cynthia

AU - Gregersen, Peter K.

AU - Zhang, Jinyi

AU - Heathcote, E. Jenny

AU - Lazaridis, Konstantinos N.

AU - Amos, Christopher I.

AU - Siminovitch, Katherine A.

N1 - Funding Information: This research was supported by grants from the Canadian Institutes for Health Research (MOP 74621), the Ontario Research Fund (RE01-061), the Canadian Primary Biliary Cirrhosis Society, the Canadian Foundation for Innovation, the Ben and Hilda Katz Charitable Foundation, the US National Institutes of Health (K23 DK68290, RO3 DK78527 and RO1 DK80670), the American Gastroenterological Association and the A.J. and Sigismunda Palumbo Charitable Trust. K.A.S. is a recipient of a Canada Research Chair award. We thank all the study subjects and supporting physicians as well as the technical staff of the University Health Network Analytical Genetics Technology Centre for their assistance in this research.

PY - 2010/8

Y1 - 2010/8

N2 - We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 × 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 × 10-13), 17q12-21 (combined P = 3.50 × 10-13) and MMEL1 (combined P = 3.15 × 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.

AB - We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 × 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 × 10-13), 17q12-21 (combined P = 3.50 × 10-13) and MMEL1 (combined P = 3.15 × 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.

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

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