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.; Nørgaard-Pedersen, Bent; Hougaard, David M.; Mors, Ole; Pedersen, Carsten B.

doi:10.1016/j.schres.2011.10.025

« Previous Next »Schizophrenia Research
Volume 134, Issue 2 , Pages 246-252, February 2012

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

Esben Agerbo
- National Centre for Register-Based Research, Aarhus University, Denmark
- Corresponding author at: National Centre for Register-based Research. Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark. Tel.: +45 89 42 68 15, +45 51 77 93 59(mobile); fax: +45 89 42 68 13.
Preben B. Mortensen
- National Centre for Register-Based Research, Aarhus University, Denmark
Carsten Wiuf
- Bioinformatics Research Centre, Aarhus University, Denmark
Michael S. Pedersen
- National Centre for Register-Based Research, Aarhus University, Denmark
John McGrath
- Queensland Brain Institute, University of Queensland, Australia
- Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Australia
Mads V. Hollegaard
- Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark
Bent Nørgaard-Pedersen
- Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark
David M. Hougaard
- Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark
Ole Mors
- Centre for Psychiatric Research, Aarhus University Hospital, Psychiatric Hospital, Denmark
Carsten B. Pedersen
- National Centre for Register-Based Research, Aarhus University, Denmark

Received 8 August 2011; received in revised form 6 October 2011; accepted 29 October 2011. published online 23 November 2011.

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.

Abbreviations: GWAS, genome-wide association studies, SNP, single-nucleotide polymorphism, PCA, principal component analysis

Keywords: Schizophrenia, Familial history of psychiatric disorder, Epidemiology, Genome-wide association, Single-nucleotide polymorphisms