Molecular Validation of the Schizophrenia Spectrum

T Bernard Bigdeli, Silviu-Alin Bacanu, Bradley T Webb, Dermot Walsh, F Anthony O'Neill, Ayman H Fanous, Brien P Riley, Kenneth S Kendler

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Background
Early descriptive work and controlled family and adoption studies support the hypothesis that a range of personality and nonschizophrenic psychotic disorders aggregate in families of schizophrenic probands. Can we validate, using molecular polygene scores from genome-wide association studies (GWAS), this schizophrenia spectrum?

Methods
The predictive value of polygenic findings reported by the Psychiatric GWAS Consortium (PGC) was applied to 4 groups of relatives from the Irish Study of High-Density Schizophrenia Families (ISHDSF; N = s) differing on their assignment within the schizophrenia spectrum. Genome-wide single nucleotide polymorphism data for affected and unaffected relatives were used to construct per-individual polygene risk scores based on the PGC stage-I results. We compared mean polygene scores in the ISHDSF with mean scores in ethnically matched population controls (N = 929). Results: The schizophrenia polygene score differed significantly across diagnostic categories and was highest in those with narrow schizophrenia spectrum, lowest in those with no psychiatric illness, and in-between in those classified in the intermediate, broad, and very broad schizophrenia spectrum. Relatives of all of these groups of affected subjects, including those with no diagnosis, had schizophrenia polygene scores significantly higher than the control sample.

Conclusions
In the relatives of high-density families, the observed pattern of enrichment of molecular indices of schizophrenia risk suggests an underlying, continuous liability distribution and validates, using aggregate common risk alleles, a genetic basis for the schizophrenia spectrum disorders. In addition, as predicted by genetic theory, nonpsychotic members of multiply-affected schizophrenia families are significantly enriched for replicated, polygenic risk variants compared with the general population.
Original languageEnglish
Pages (from-to)60-65
JournalSchizophrenia Bulletin
Volume40
Issue number1
DOIs
Publication statusPublished - 22 Aug 2013

ASJC Scopus subject areas

  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Molecular Validation of the Schizophrenia Spectrum'. Together they form a unique fingerprint.

Cite this