title: Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls.
abstract: OBJECTIVE
  The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls.
  
  
  METHODS
  Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers. The levels of anti-citrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), anti-tissue transglutaminase antibodies (AGTAs), and anti-thyroid peroxidase (anti-TPO) antibodies were measured. All subjects were genotyped for autoimmune risk alleles, and the association between number of autoimmune risk alleles present and number of types of autoantibodies present was studied. A phenome-wide association study (PheWAS) was conducted to study potential associations between autoantibodies and clinical diagnoses among RA cases and non-RA controls.
  
  
  RESULTS
  The mean ages were 60.7 years in RA cases and 64.6 years in non-RA controls. The proportion of female subjects was 79% in each group. The prevalence of ACPAs and ANAs was higher in RA cases compared to controls (each P < 0.0001); there were no differences in the prevalence of anti-TPO antibodies and AGTAs. Carriage of higher numbers of autoimmune risk alleles was associated with increasing numbers of autoantibody types in RA cases (P = 2.1 × 10(-5)) and non-RA controls (P = 5.0 × 10(-3)). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjögren's/sicca syndrome in RA cases.
  
  
  CONCLUSIONS
  The increased frequency of autoantibodies in RA cases and non-RA controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS of EMR data, with linkage to laboratory data obtained from blood samples, provide a novel method to test for the clinical significance of biomarkers in disease.
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street, PBB-B3, Boston, MA 02115, USA. kliao@partners.org
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Liao
authors.forename: Fina
authors.initials: F
authors.lastname: Kurreeman
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Grant
authors.initials: G
authors.lastname: Duclos
authors.forename: Shawn
authors.initials: S
authors.lastname: Murphy
authors.forename: Raul
authors.initials: R
authors.lastname: Guzman
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.forename: Namrata
authors.initials: N
authors.lastname: Gupta
authors.forename: Vivian
authors.initials: V
authors.lastname: Gainer
authors.forename: Peter
authors.initials: P
authors.lastname: Schur
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.forename: Peter
authors.initials: P
authors.lastname: Szolovits
authors.forename: Susanne
authors.initials: S
authors.lastname: Churchill
authors.forename: Isaac
authors.initials: I
authors.lastname: Kohane
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
mesh_terms: D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics; D057286:Electronic Health Records; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007037:Hypothyroidism / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012859:Sjogren's Syndrome / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D013966:Thyroiditis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D007453:Iodide Peroxidase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins