title: Genetic insights into common pathways and complex relationships among immune-mediated diseases.
abstract: Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.
authors.affiliation: 1] Inflammatory Bowel Disease Research Group, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK. [2].
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
authors.forename: Adrian
authors.initials: A
authors.lastname: Cortes
authors.forename: David A
authors.initials: DA
authors.lastname: van Heel
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D004777:Environment; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics* / Q000378:metabolism*; D040641:Quantitative Trait Loci; D015398:Signal Transduction
references.citation: Nat Genet. 2012 Jan 29;44(3):291-6
references.pmid: 22286218
references.citation: Nature. 2007 Dec 6;450(7171):887-92
references.pmid: 18004301
references.citation: Nature. 2001 May 31;411(6837):599-603
references.pmid: 11385576
references.citation: Science. 2009 Apr 17;324(5925):387-9
references.pmid: 19264985
references.citation: Eur J Hum Genet. 2010 Apr;18(4):502-4
references.pmid: 19888296
references.citation: Am J Hum Genet. 2012 Jan 13;90(1):7-24
references.pmid: 22243964
references.citation: Nat Genet. 2009 Sep;41(9):1011-5
references.pmid: 19701192
references.citation: Ann Rheum Dis. 2011 Mar;70(3):508-11
references.pmid: 21149499
references.citation: Nat Genet. 2010 Jul;42(7):570-5
references.pmid: 20562874
references.citation: Nature. 2012 Aug 23;488(7412):508-511
references.pmid: 22801493
references.citation: Arthritis Rheum. 1987 Nov;30(11):1205-13
references.pmid: 2446635
references.citation: Nature. 2007 Aug 30;448(7157):1058-62
references.pmid: 17676033
references.citation: Nat Genet. 2012 Mar 25;44(5):483-9
references.pmid: 22446960
references.citation: Hum Mol Genet. 2012 Dec 1;21(23):5185-92
references.pmid: 22914738
references.citation: Nat Genet. 2012 Dec;44(12):1336-40
references.pmid: 23143596
references.citation: Nat Genet. 2012 Dec;44(12):1341-8
references.pmid: 23143594
references.citation: Nat Immunol. 2011 Mar;12(3):231-8
references.pmid: 21240265
references.citation: Nat Genet. 2011 Jul 10;43(8):761-7
references.pmid: 21743469
references.citation: Immunol Rev. 2010 Jan;233(1):34-54
references.pmid: 20192991
references.citation: Nature. 2001 May 31;411(6837):603-6
references.pmid: 11385577
references.citation: PLoS One. 2010 Sep 09;5(9):
references.pmid: 20844740
references.citation: Nat Genet. 2011 Oct 09;43(11):1066-73
references.pmid: 21983784
references.citation: Eur J Hum Genet. 2005 Nov;13(11):1223-30
references.pmid: 16106256
references.citation: Nature. 1973 Mar 9;242(5393):121
references.pmid: 4694299
references.citation: Nat Genet. 2007 Nov;39(11):1329-37
references.pmid: 17952073
references.citation: Nat Genet. 2007 Feb;39(2):207-11
references.pmid: 17200669
references.citation: N Engl J Med. 1973 Apr 5;288(14):704-6
references.pmid: 4688372
references.citation: Nat Genet. 2003 Aug;34(4):395-402
references.pmid: 12833157
references.citation: Genes Immun. 2009 Dec;10 Suppl 1:S85-94
references.pmid: 19956107
references.citation: Blood. 2011 Feb 17;117(7):2227-36
references.pmid: 21088135
references.citation: N Engl J Med. 2011 Jul 14;365(2):127-38
references.pmid: 21524210
references.citation: Arthritis Rheum. 2009 Sep;60(9):2845-7
references.pmid: 19714648
references.citation: Nat Genet. 2012 May 06;44(6):676-80
references.pmid: 22561518
references.citation: PLoS One. 2010 Oct 26;5(10):e13454
references.pmid: 21049023
references.citation: N Engl J Med. 2012 Jul 19;367(3):214-23
references.pmid: 22808956
references.citation: PLoS One. 2011 Feb 22;6(2):e17160
references.pmid: 21364948
references.citation: Nat Genet. 2006 Aug;38(8):917-20
references.pmid: 16845398
references.citation: Genes Immun. 2010 Sep;11(6):490-6
references.pmid: 20463747
references.citation: Nat Genet. 2010 Apr;42(4):295-302
references.pmid: 20190752
references.citation: Lancet. 1973 Apr 28;1(7809):904-7
references.pmid: 4123836
references.citation: Arthritis Rheum. 2002 Dec;46(12):3143-50
references.pmid: 12483717
references.citation: Nat Genet. 2011 Nov 06;43(12):1193-201
references.pmid: 22057235
references.citation: Nat Genet. 2013 Jul;45(7):730-8
references.pmid: 23749187
references.citation: Nat Genet. 2013 Feb;45(2):124-30
references.pmid: 23263488
references.citation: Nat Rev Rheumatol. 2013 Jun;9(6):375-9
references.pmid: 23229447
references.citation: Eur J Hum Genet. 2009 Oct;17(10):1309-13
references.pmid: 19293837
references.citation: Nat Genet. 2010 Nov;42(11):985-90
references.pmid: 20953190
references.citation: Genome Res. 2012 Sep;22(9):1790-7
references.pmid: 22955989
references.citation: Am J Hum Genet. 2007 Feb;80(2):273-90
references.pmid: 17236132
references.citation: N Engl J Med. 2009 Nov 19;361(21):2033-45
references.pmid: 19890111
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: Nat Genet. 2012 Oct;44(10):1137-41
references.pmid: 22961000
references.citation: Nat Genet. 2001 Sep;29(1):19-20
references.pmid: 11528384
references.citation: Nat Genet. 2007 May;39(5):596-604
references.pmid: 17435756
references.citation: Nat Genet. 2009 Dec;41(12):1319-24
references.pmid: 19898480
references.citation: Am J Hum Genet. 2004 Aug;75(2):330-7
references.pmid: 15208781
references.citation: Nat Genet. 2012 Dec;44(12):1294-301
references.pmid: 23104008
references.citation: Arthritis Rheum. 2006 Sep;54(9):2817-29
references.pmid: 16947782
references.citation: Ann Clin Res. 1975 Oct;7(5):301-11
references.pmid: 1211846
references.citation: Immunol Rev. 1999 Feb;167:257-74
references.pmid: 10319267
references.citation: Curr Dir Autoimmun. 2004;7:98-132
references.pmid: 14719377
references.citation: Nat Genet. 2011 Mar;43(3):253-8
references.pmid: 21336280
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15040-4
references.pmid: 17855560
references.citation: Tissue Antigens. 1976 Aug;8(2):95-9
references.pmid: 968901
references.citation: Nat Genet. 2006 Jun;38(6):617-9
references.pmid: 16699517
references.citation: Arthritis Res Ther. 2011 Feb 01;13(1):101
references.pmid: 21345260
references.citation: Brain. 2011 Mar;134(Pt 3):653-64
references.pmid: 21303861
references.citation: Hum Genet. 1998 Oct;103(4):475-82
references.pmid: 9856493
references.citation: Nat Genet. 2007 Jul;39(7):830-2
references.pmid: 17554261
references.citation: Am J Hum Genet. 2004 Sep;75(3):504-7
references.pmid: 15273934
references.citation: PLoS Genet. 2010 Oct 14;6(10):e1001157
references.pmid: 20976248
references.citation: Nat Genet. 2011 Aug 14;43(9):908-12
references.pmid: 21841782
references.citation: Hum Mol Genet. 2010 Dec 1;19(23):4705-14
references.pmid: 20843824
references.citation: Arthritis Rheum. 2007 Aug;56(8):2633-9
references.pmid: 17665420
references.citation: Nat Genet. 2010 Dec;42(12):1118-25
references.pmid: 21102463
references.citation: Nat Genet. 2011 Aug 14;43(9):902-7
references.pmid: 21841778
references.citation: Arthritis Rheum. 2004 Oct;50(10):3085-92
references.pmid: 15476204
references.citation: Gut. 2012 Dec;61(12):1693-700
references.pmid: 22595313
references.citation: Am J Hum Genet. 2008 May;82(5):1202-10
references.pmid: 18439550
references.citation: Nature. 2009 Oct 8;461(7265):747-53
references.pmid: 19812666
references.citation: PLoS Genet. 2013;9(2):e1003222
references.pmid: 23441136
references.citation: Lancet. 2006 Feb 25;367(9511):668-78
references.pmid: 16503465
references.citation: Am J Hum Genet. 1986 Feb;38(2):170-87
references.pmid: 3456197
references.citation: Nat Genet. 2013 Feb;45(2):202-7
references.pmid: 23291587
references.citation: Nat Rev Immunol. 2012 Nov;12(11):774-85
references.pmid: 23059429
references.citation: Nat Immunol. 2011 Oct 23;12(12):1184-93
references.pmid: 22019834
references.citation: Nat Genet. 2009 Dec;41(12):1330-4
references.pmid: 19915572
references.citation: PLoS Genet. 2009 Jun;5(6):e1000534
references.pmid: 19557189
references.citation: Nat Genet. 2012 Mar 25;44(5):502-10
references.pmid: 22446964
references.citation: Science. 2006 Dec 1;314(5804):1461-3
references.pmid: 17068223
references.citation: Nat Genet. 2008 Nov;40(11):1319-23
references.pmid: 18836448
references.citation: Nat Genet. 2004 Apr;36(4):337-8
references.pmid: 15004560