title: Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?
abstract: OBJECTIVE
  To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases.
  
  
  METHODS
  A population-based cohort of parent-offspring triads from Denmark (1977-2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history.
  
  
  RESULTS
  Among 3 513 817 parent-offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS).
  
  
  CONCLUSIONS
  The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.
authors.affiliation: Correspondence to Emily C Somers, University of Michigan, Division of Rheumatology, 24 Frank Lloyd Wright Drive, PO Box 481, Ann Arbor, Michigan 48109-5358, USA. emsomers@umich.edu
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.forename: Sussie
authors.initials: S
authors.lastname: Antonsen
authors.forename: Lars
authors.initials: L
authors.lastname: Pedersen
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D001171:Arthritis, Juvenile / Q000453:epidemiology* / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics*; D016241:Child of Impaired Parents / Q000706:statistics & numerical data; D041321:Chromosomes, Human, X / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D010290:Parents; D012307:Risk Factors; D017678:Sex Distribution