Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: a Danish national birth cohort-based study

Agerbo, Esben, Mortensen, Preben B., Wiuf, Carsten, Pedersen, Michael S., McGrath, John, Hollegaard, Mads V., Norgaard-Pedersen, Bent, Hougaard, David M., Mors, Ole and Pedersen, Carsten B. (2012) Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: a Danish national birth cohort-based study. Schizophrenia Research, 134 2-3: 246-252. doi:10.1016/j.schres.2011.10.025


Author Agerbo, Esben
Mortensen, Preben B.
Wiuf, Carsten
Pedersen, Michael S.
McGrath, John
Hollegaard, Mads V.
Norgaard-Pedersen, Bent
Hougaard, David M.
Mors, Ole
Pedersen, Carsten B.
Title Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: a Danish national birth cohort-based study
Journal name Schizophrenia Research   Check publisher's open access policy
ISSN 0920-9964
1573-2509
Publication date 2012-02
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.schres.2011.10.025
Volume 134
Issue 2-3
Start page 246
End page 252
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2012
Language eng
Formatted 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.

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.
Keyword Schizophrenia
Familial history of psychiatric disorder
Epidemiology
Genome-wide association
Single-nucleotide polymorphisms
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 21 November 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
 
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Created: Wed, 07 Dec 2011, 09:22:00 EST by Debra McMurtrie on behalf of Queensland Brain Institute