Genetics in PBC: What Do the “Risk Genes” Teach Us?

Clinical Reviews in Allergy and Immunology

Volumn 48, Issue 2-3, 2015, Pages 176-181

  Hirschfield, Gideon M ^a   Siminovitch, Katherine A ^b  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b MOUNT SINAI HOSPITAL   (Canada)

Author keywords

Autoimmune liver disease; Genetics; Primary biliary cirrhosis

Indexed keywords

HLA ANTIGEN;

AUTOIMMUNE DISEASE; BILIARY CIRRHOSIS; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETICS; HUMAN; IMMUNOLOGY; RISK FACTOR;

AUTOIMMUNE DISEASES; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HLA ANTIGENS; HUMANS; LIVER CIRRHOSIS, BILIARY; RISK FACTORS;

EID: 84939893722     PISSN: 10800549     EISSN: 15590267     Source Type: Journal    
DOI: 10.1007/s12016-014-8419-x     Document Type: Review

References (27)

1. Trivedi PJ, Hirschfield GM (2012) Review article: overlap syndromes and autoimmune liver disease. Aliment Pharmacol Ther 36:517–533
2. Hirschfield GM, Gershwin ME (2013) The immunobiology and pathophysiology of primary biliary cirrhosis. Annu Rev Pathol 8:303–330
3. Hirschfield GM, Karlsen TH, Lindor KD et al (2013) Primary sclerosing cholangitis. Lancet 382:1587–1599
4. Mells GF, Kaser A, Karlsen TH (2013) Novel insights into autoimmune liver diseases provided by genome-wide association studies. J Autoimmun 46:41–54
5. Hirschfield GM, Chapman RW, Karlsen TH et al (2013) The genetics of complex cholestatic disorders. Gastroenterology 144:1357–1374
6. Romeo S, Kozlitina J, Xing C et al (2008) Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:1461–1465
7. Chalasani N, Guo X, Loomba R et al (2010) Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease. Gastroenterology 139:1567–1576
8. Kozlitina J, Smagris E, Stender S et al (2014) Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. doi:10.1038/ng.2901
9. Nakamura M, Nishida N, Kawashima M et al (2012) Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. Am J Hum Genet 91:721–728
10. Anstee QM, Knapp S, Maguire EP et al (2013) Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition. Nat Commun 4:2816
11. Smemo S, Tena JJ, Kim K-H, et al (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature; advance online publication
12. Ragvin A, Moro E, Fredman D et al (2010) Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3. Proc Natl Acad Sci U S A 107:775–780
13. Juran BD, Hirschfield GM, Invernizzi P et al (2012) Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants. Hum Mol Genet 21:5209–5221
14. Lee MN, Ye C, Villani AC et al (2014) Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science 343:1246980
15. Fairfax BP, Humburg P, Makino S et al (2014) Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science 343:1246949
16. Trowsdale J, Knight JC (2013) Major histocompatibility complex genomics and human disease. Annu Rev Genomics Hum Genet 14:301–323
17. Invernizzi P (2011) Human leukocyte antigen in primary biliary cirrhosis: an old story now reviving. Hepatology 54:714–723
18. Hirschfield GM, Liu X, Xu C et al (2009) Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med 360:2544–2555
19. Liu X, Invernizzi P, Lu Y et al (2010) Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet 42:658–660
20. Mells GF, Floyd JA, Morley KI et al (2011) Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 43:329–332
21. Walker EJ, Hirschfield GM, Xu C et al (2009) CTLA4/ICOS gene variants and haplotypes are associated with rheumatoid arthritis and primary biliary cirrhosis in the Canadian population. Arthritis Rheum 60:931–937
22. Hirschfield GM, Liu X, Han Y et al (2010) Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat Genet 42:655–657
23. Hirschfield GM, Xie G, Lu E et al (2012) Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes Immun 13:328–335
24. Liu JZ, Almarri MA, Gaffney DJ et al (2012) Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat Genet 44:1137–1141
25. Hirschfield GM, Heathcote EJ, Gershwin ME (2010) Pathogenesis of cholestatic liver disease and therapeutic approaches. Gastroenterology 139:1481–1496
26. Okada Y, Wu D, Trynka G et al (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506:376–381
27. Wong A, Ma BB (2014) Personalizing therapy for colorectal cancer. Clin Gastroenterol Hepatol 12:139–144