title: Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history.
abstract: OBJECTIVE
  To develop and validate rheumatoid arthritis (RA) risk models based on family history, epidemiologic factors and known genetic risk factors.
  
  
  METHODS
  We developed and validated models for RA based on known RA risk factors, among women in two cohorts: the Nurses' Health Study (NHS, 381 RA cases and 410 controls) and the Epidemiological Investigation of RA (EIRA, 1244 RA cases and 971 controls). Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in logistic regression models for the study population and for those with positive family history. The joint effect of family history with genetics, smoking and body mass index (BMI) was evaluated using logistic regression models to estimate ORs for RA.
  
  
  RESULTS
  The complete model including family history, epidemiologic risk factors and genetics demonstrated AUCs of 0.74 for seropositive RA in NHS and 0.77 for anti-citrullinated protein antibody (ACPA)-positive RA in EIRA. Among women with positive family history, discrimination was excellent for complete models for seropositive RA in NHS (AUC 0.82) and ACPA-positive RA in EIRA (AUC 0.83). Positive family history, high genetic susceptibility, smoking and increased BMI had an OR of 21.73 for ACPA-positive RA.
  
  
  CONCLUSIONS
  We developed models for seropositive and seronegative RA phenotypes based on family history, epidemiological and genetic factors. Among those with positive family history, models using epidemiologic and genetic factors were highly discriminatory for seropositive and seronegative RA. Assessing epidemiological and genetic factors among those with positive family history may identify individuals suitable for RA prevention strategies.
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sparks
authors.affiliation: Harvard School of Public Health and Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.affiliation: Research Institute, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Linda T
authors.initials: LT
authors.lastname: Hiraki
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Malspeis
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Costenbader
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
mesh_terms: D000368:Aged; D000428:Alcohol Drinking; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D015992:Body Mass Index; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; C058222:2-amino-5-hydroxy-4-oxopentanoic acid; D000622:Aminolevulinic Acid
keywords: Epidemiology; Gene Polymorphism; Rheumatoid Arthritis