title: Familial aggregation of schizophrenia: the moderating effect of age at onset, parental immigration, paternal age and season of birth.
abstract: OBJECTIVE
  An abundance of evidence has firmly established the familial aggregation of schizophrenia. The aim of this study was to examine how age at onset, parental characteristics and season of birth modify the familiality in schizophrenia.
  
  
  METHODS
  A population-based cohort was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. Among 5,075,998 full siblings born between 1932 through to 1990, 16,346 cases of schizophrenia were identified. Familial aggregation was measured by the sibling recurrence-risk ratio, defined as the risk of schizophrenia among full siblings of schizophrenia patients compared with the risk among siblings of unaffected people.
  
  
  RESULTS
  We found a statistically significantly lower recurrence-risk ratio in siblings of later onset cases (7.2; 95% confidence interval (95% CI) 6.7-7.9) than of early onset cases (10.8; 95% CI 9.4-12.2). A lower recurrence-risk ratio was observed among offspring to fathers above 40 years (6.3; 95% CI 5.3-7.3) as compared with offspring of younger fathers (8.6; 95% CI 8.0-9.3). Further, among offspring to parents born outside Sweden the recurrence-risk ratio was statistically significantly lower (maternal immigrants 4.8; 95% CI 4.0-5.7, paternal immigrants 5.7; 95% CI 4.6-6.9) than among offspring to parents born in Sweden.
  
  
  CONCLUSIONS
  The familial aggregation of schizophrenia was reduced by higher age at onset, advancing paternal age and immigrant status of parents.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Anna.Svensson@ki.se
authors.forename: Anna C
authors.initials: AC
authors.lastname: Svensson
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: Sven
authors.initials: S
authors.lastname: Sandin
authors.forename: Sara
authors.initials: S
authors.lastname: Öberg
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004641:Emigration and Immigration / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010290:Parents; D036801:Parturition; D010331:Paternal Age; D010375:Pedigree; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D012621:Seasons; D035781:Siblings; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult