Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

Article metrics


A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Results of genome-wide association tests for PBC.


  1. 1

    Gershwin, M.E. & Mackay, I.R. Hepatology 47, 737–745 (2008).

  2. 2

    Hirschfield, G.M. et al. N. Engl. J. Med. 360, 2544–2555 (2009).

  3. 3

    Invernizzi, P. et al. Hepatology 48, 1906–1912 (2008).

  4. 4

    Moffatt, M.F. et al. Nature 448, 470–473 (2007).

  5. 5

    McGovern, D.P. et al. Nat. Genet. 42, 332–337 (2010).

  6. 6

    Barrett, J.C. et al. Nat. Genet. 41, 703–707 (2009).

  7. 7

    Romero, F., Martinez, A.C., Camonis, J. & Rebollo, A. EMBO J. 18, 3419–3430 (1999).

  8. 8

    Wang, J.H. et al. Immunity 9, 543–553 (1998).

  9. 9

    Sun, J., Matthias, G., Mihatsch, M.J., Georgopoulos, K. & Matthias, P. J. Immunol. 170, 1699–1706 (2003).

  10. 10

    Garrett-Sinha, L.A. et al. Immunity 10, 399–408 (1999).

  11. 11

    Dontje, W. et al. Blood 107, 2446–2452 (2006).

  12. 12

    Nguyen, V.T. & Benveniste, E.N. J. Biol. Chem. 275, 23674–23684 (2000).

  13. 13

    Remmers, E.F. et al. N. Engl. J. Med. 357, 977–986 (2007).

  14. 14

    Sleiman, P.M. et al. N. Engl. J. Med. 362, 36–44 (2010).

  15. 15

    Guo, F., Velu, C.S., Grimes, H.L. & Zheng, Y. Blood 114, 2909–2916 (2009).

Download references


We thank the subjects and physicians who contributed DNA samples and clinical data for this study. This work was supported in part by the US National Institutes of Health (R01 DK056839, R01 DK80670, K23 DK68290 and RO3 DK78527), the Canadian Institutes for Health Research (MOP 74621), the Ontario Research Fund (RE01-061), the Canadian Primary Biliary Cirrhosis Society, the American Gastroenterological Association and the A.J. and Sigismunda Palumbo Charitable Trust.

Author information

X.L., P.I., Yue Lu and R.K. contributed to initial data analyses and manuscript preparation. P.I., R.S., C.S. and A.L. managed DNA samples. A.L., F. Macciardi, A.T.L. and P.K.G. performed genotyping. M.R. provided database management. P.I., Yan Lu, I.B., M.P., C.X., G.X., A.L.M., R.P.M., K.M.P., C.N.G., F.B., M.Z., E.J.H., S.L., F.R., E.B., A.F., R.L., G.N., A.A., L. Muratori, P.M., P.L.A., P.A., M. Margotti, M.B., B.C., D.A., M.C.B., F. Marra, A. Pisano, C.R., M.C., M. Marzioni, A.B., L.F., M.S., P.P., V.O.P., C.T., L.C., S.B., S.R., M.V., C.P., A.M., P.T., A. Picciotto, A.G., C.F., S.C., G.C., L. Morini, N.C., A.C., G.S. and R.M. contributed to experimental design, subject assessment and sample collection. P.I., G.M.H., K.A.S., C.I.A., M.E.G. and M.F.S. contributed to experimental design and interpretation, statistical analyses, and initial manuscript preparation. All authors contributed to the final paper.

Correspondence to Michael F Seldin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1 and 2, Supplementary Tables 1–5 and Supplementary Methods (PDF 439 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liu, X., Invernizzi, P., Lu, Y. et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 42, 658–660 (2010) doi:10.1038/ng.627

Download citation

Further reading