“… wise, amazed, temp’rate, and furious, Loyal and neutral, in a moment”: first heritability analysis of affective temperaments reports remarkably high SNP-based heritability

Introduction Depression shows a moderate heritability of 37-42%, which can be up to 75% in severely depressed samples 75%. At the same time SNP-based depression GWAS-s is around 8-9%. Heterogeneity depressive phenotype may contribute not only lack understanding its genetic background but also hinder identification novel targets. Thus clinically relevant intermediate endophenotypes are needed for. The affective temperaments Akiskal model considered high-risk states or subclinical manifestations mood disorders. Considering their strong and biological background, high family studies, temporal stability, they prove for depression. Objectives aim current study was investigate determinants based on GWAS approach. Methods 775 subjects aged between 18-60 years recruited Budapest, Hungary provided completed questionnaires including TEMPS-A (Temperament Evaluation Memphis, Pisa, Paris San Diego) scale. A genome-wide association analysis performed with five as outcome variables. Age, gender, top 10 principal components genome, other 4 were added covariates. Summary statistics derived from analyses used estimate heritability, i.e. variance explained by different temperaments. LD score regression using LDPred2 [4] beta values effect size case all 5 temperament phenotypes. Results rs3798978 showed significance (p=4.44x10-8) anxious temperament, several variants suggestive significances highest estimated (h2 = 0.5224) observed similarly hyperthymic 0.4956). Anxious cyclothymic almost (cyclothymic h2 0.1651, 0.1663), whereas irritable we got negative estimation -0.0567), means that phenotypic environmental factors. Conclusions Our yielded remarkably explaining 52% 50% variances. In contrast 8-9% studies our findings suggest these Disclosure Interest None Declared