TY - JOUR
T1 - Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia
T2 - a Danish national birth cohort-based study
AU - Agerbo, Esben
AU - Mortensen, Preben Bo
AU - Wiuf, Carsten
AU - Pedersen, Michael S
AU - McGrath, John
AU - Hollegaard, Mads Vilhelm
AU - Nørgaard-Pedersen, Bent
AU - Hougaard, David M
AU - Mors, Ole
AU - Pedersen, Carsten B
N1 - Copyright © 2011 Elsevier B.V. All rights reserved.
PY - 2012/2
Y1 - 2012/2
N2 - 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. Method: 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.
AB - 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. Method: 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.
KW - Cohort Studies
KW - Community Health Planning
KW - Denmark
KW - Family Health
KW - Female
KW - Genetic Predisposition to Disease
KW - Genetics, Population
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Psychotic Disorders
KW - Risk
KW - Schizophrenia
U2 - 10.1016/j.schres.2011.10.025
DO - 10.1016/j.schres.2011.10.025
M3 - Journal article
C2 - 22108675
SN - 0920-9964
VL - 134
SP - 246
EP - 252
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 2-3
ER -