The current study examined quantitative measures of psychosis proneness in a nonpsychotic
population, in order to elucidate their underlying genetic architecture and to observe
if there is any commonality to that already detected in the studies of individuals with overt
psychotic conditions, such as schizophrenia and bipolar disorder.
Heritability, univariate and multivariate genome-wide association tests, including a series of
comprehensive gene-based association analyses, were developed in 4269 non-psychotic
persons participating in the Northern Finland Birth Cohort 1966 study with information on the
following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical
and Social Anhedonia (a.k.a. Chapman’s Schizotypia scales), and Schizoidia scale. Genomewide
genetic data was available for ~9.84 million SNPs.
Heritability estimates ranged from 16% to 27%. Phenotypic, genetic and environmental
correlations ranged from 0.04-0.43, 0.25-0.73, and 0.12-0.43, respectively. Univariate GWAS
tests revealed an intronic SNP (rs12449097) at the TMC7 gene (16p12.3) that significantly
associated (p=3.485 × 10-8) with the hypomanic scale. Bivariate GWAs tests including the
hypomanic and physical anhedonia scales suggested a further borderline significant SNP
(rs188320715; p-value=5.261 × 10-8, ~572kb downstream the ARID1B gene at 6q25.3).
Gene-based tests highlighted 20 additional genes of which 5 had previously been associated
to schizophrenia and/or bipolar disorder: CSMD1, CCDC141, SLC1A2, CACNA1C and
SNAP25. Altogether the findings explained from 3.7% to 14.1% of the corresponding trait
heritability.
In conclusion, this study provides preliminary genomic evidence suggesting that qualitatively
similar biological factors may underlie different psychosis proneness measures, some of
which could further predispose to schizophrenia and bipolar disorder.