title: High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.
abstract: Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Eyre
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.forename: Dorothée
authors.initials: D
authors.lastname: Diogo
authors.forename: Annette
authors.initials: A
authors.lastname: Lee
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.forename: Eli
authors.initials: E
authors.lastname: Stahl
authors.forename: Sebastien
authors.initials: S
authors.lastname: Viatte
authors.forename: Kate
authors.initials: K
authors.lastname: McAllister
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Gosia
authors.initials: G
authors.lastname: Trynka
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Westra
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Xinli
authors.initials: X
authors.lastname: Hu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Sandor
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Sonia
authors.initials: S
authors.lastname: Davila
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Khai Koon
authors.initials: KK
authors.lastname: Heng
authors.forename: Robert
authors.initials: R
authors.lastname: Andrews
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hunt
authors.forename: Cordelia
authors.initials: C
authors.lastname: Langford
authors.forename: Deborah
authors.initials: D
authors.lastname: Symmons
authors.forename: Pat
authors.initials: P
authors.lastname: Concannon
authors.forename: Suna
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Ärlsetig
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood / Q000235:genetics; D002874:Chromosome Mapping / Q000295:instrumentation / Q000379:methods*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D001323:Autoantibodies