title: Newly identified genetic risk variants for celiac disease related to the immune response.
abstract: Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.
authors.affiliation: Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, UK.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hunt
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.forename: Graham
authors.initials: G
authors.lastname: Turner
authors.forename: Graham A R
authors.initials: GA
authors.lastname: Heap
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.forename: Marcel
authors.initials: M
authors.lastname: Bruinenberg
authors.forename: Jihane
authors.initials: J
authors.lastname: Romanos
authors.forename: Lotte C
authors.initials: LC
authors.lastname: Dinesen
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Ryan
authors.forename: Davinder
authors.initials: D
authors.lastname: Panesar
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.forename: William M
authors.initials: WM
authors.lastname: McLaren
authors.forename: Geoffrey K T
authors.initials: GK
authors.lastname: Holmes
authors.forename: Peter D
authors.initials: PD
authors.lastname: Howdle
authors.forename: Julian R F
authors.initials: JR
authors.lastname: Walters
authors.forename: David S
authors.initials: DS
authors.lastname: Sanders
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Playford
authors.forename: Gosia
authors.initials: G
authors.lastname: Trynka
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
authors.forename: Wieke H M
authors.initials: WH
authors.lastname: Verbeek
authors.forename: Valerie
authors.initials: V
authors.lastname: Trimble
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Stevens
authors.forename: Colm
authors.initials: C
authors.lastname: O'Morain
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Kennedy
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pennington
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Martin C
authors.initials: MC
authors.lastname: Wapenaar
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Ralph
authors.initials: R
authors.lastname: McGinnis
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: David A
authors.initials: DA
authors.lastname: van Heel
mesh_terms: D000818:Animals; D015415:Biomarkers; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006683:HLA-DQ Antigens / Q000378:metabolism; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D053728:Interleukin-18 Receptor beta Subunit / Q000097:blood / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054397:Receptors, CCR3 / Q000235:genetics; D012307:Risk Factors; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D006683:HLA-DQ Antigens; C508858:IL12A protein, human; C115629:IL18RAP protein, human; D053765:Interleukin-12 Subunit p35; D053728:Interleukin-18 Receptor beta Subunit; D020710:RGS Proteins; C080831:RGS1 protein, human; D012333:RNA, Messenger; D054397:Receptors, CCR3