Genome‐wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Bigdeli, T. B. and Ripke, S. and Bacanu, S. A. and Lee, S. H. and Wray, N. R. and Gejman, P. V. and Rietschel, M. and Cichon, S. and St Clair, D. and Corvin, A. and Kirov, G. and McQuillin, A. and Gurling, H. and Rujescu, D. and Andreassen, O. A. and Werge, T. and Blackwood, D. H. and Pato, C. N. and Pato, M. T. and Malhotra, A. K. and O'Donovan, M. C. and Kendler, K. S. and Fanous, A. H. and Schizophrenia Working Group of the Psychiatric Genomics, Consortium. (2016) Genome‐wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness. American Journal of Medical Genetics; Part B: Neuropsychiatric Genetics, 171B (2). pp. 276-289.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61528/

Downloads: Statistics Overview


Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N = 978), cases reporting no such family history (N = 4,503), and unscreened controls (N = 8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R(2 ) = 0.0021; P = 0.00331; P-value threshold >0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P = 0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:05 Mar 2019 19:04
Deposited On:05 Mar 2019 19:04

Repository Staff Only: item control page