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

26663532

DOI

10.1002/ajmg.b.32402