title: Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: a Danish national birth cohort-based study.
abstract: BACKGROUND
  Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder.
  
  
  METHODS
  A nested case-control study with 739 cases with schizophrenia and 800 controls. Their parents and siblings. Information from national health registers and GWAS data from the national neonatal biobank.
  
  
  RESULTS
  Offspring schizophrenia risk was elevated in those whose mother, father or siblings had been diagnosed with schizophrenia or related psychosis, bipolar affective disorder or any other psychiatric disorder. The rate ratio was 9.31 (3.85; 22.44) in offspring whose 1st degree relative was diagnosed with schizophrenia. This rate ranged between 8.31 and 11.34 when adjusted for each SNP individually and shrank to 8.23 (3.13; 21.64) when adjusted for 25% of the SNP-variation in candidate genes. The percentage of the excess risk associated with a family history of schizophrenia mediated through genome-wide SNP-variation ranged between -6.1%(-17.0%;2.6%) and 4.1%(-3.9%;15.2%). Analogous results were seen for each parent and for histories of bipolar affective and other psychiatric diagnoses.
  
  
  CONCLUSIONS
  The excess risk of schizophrenia in offspring of parents who have a psychotic, bipolar affective or other psychiatric disorder is not currently explained by the SNP variation included in this study in accordance with findings from published genetic studies.
authors: National Centre for Register-Based Research, Aarhus University, Denmark. ea@ncrr.dk
authors: Esben
authors: E
authors: Agerbo
authors: Preben B
authors: PB
authors: Mortensen
authors: Carsten
authors: C
authors: Wiuf
authors: Michael S
authors: MS
authors: Pedersen
authors: John
authors: J
authors: McGrath
authors: Mads V
authors: MV
authors: Hollegaard
authors: Bent
authors: B
authors: Nørgaard-Pedersen
authors: David M
authors: DM
authors: Hougaard
authors: Ole
authors: O
authors: Mors
authors: Carsten B
authors: CB
authors: Pedersen
mesh_terms: D015331:Cohort Studies; D018672:Community Health Planning; D003718:Denmark / Q000453:epidemiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*