Genome-wide association study of psychosis proneness in the Finnish population

• Published in: Schizophrenia Bulletin
• Main Authors: Ortega-Alonso, A, Ekelund, J, Sarin, A, Miettunen, J, Veijola, J, Jarvelin, M, Hennah, W
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: Oxford University Press (OUP) 2017
• Subjects: Finnish population; bipolar disorder; genome-wide association study; heritability; psychoses proneness; schizophrenia; 11 Medical And Health Sciences; 17 Psychology And Cognitive Sciences; Psychiatry; Northern Finland
• Online Access: http://hdl.handle.net/10044/1/43916; https://doi.org/10.1093/schbul/sbx006

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.