Title
Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness
Publication Date
2016
Journal Title
Am J Med Genet B Neuropsychiatr Genet
Abstract
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 R2 = 0.0021; P = 0.00331; P-value threshold
Volume Number
171
Issue Number
2
Pages
276-89
Document Type
Article
EPub Date
2015/12/15
Status
Faculty, Northwell Researcher
Facility
School of Medicine; Northwell Health
Primary Department
Psychiatry
Additional Departments
Molecular Medicine
PMID
DOI
10.1002/ajmg.b.32402