title: Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden.
abstract: OBJECTIVE
  Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease.
  
  
  METHODS
  Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register.
  
  
  RESULTS
  Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk.
  
  
  CONCLUSIONS
  Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-5735-9626
authors.initials: T
authors.lastname: Frisell
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden Rheumatology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Hellgren
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester, UK.
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden Rheumatology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
mesh_terms: D000328:Adult; D001168:Arthritis / Q000453:epidemiology / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012042:Registries; D012217:Rheumatoid Factor / Q000097:blood; D018570:Risk Assessment / Q000379:methods; D013548:Sweden / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
keywords: Ant-CCP; Arthritis; Autoimmune Diseases; Rheumatoid Arthritis; Rheumatoid Factor