title: To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?
abstract: OBJECTIVE
  Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors.
  
  
  METHODS
  History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]).
  
  
  RESULTS
  Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35).
  
  
  CONCLUSIONS
  Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Thomas
authors.initials: T
authors.lastname: Frisell
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Källberg
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D004522:Educational Status; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010298:Parity; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D012822:Silicon Dioxide / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013548:Sweden / Q000453:epidemiology
chemical_list: D012822:Silicon Dioxide