PhD Scientific Days 2024

Mental Health Sciences III.

Investigating the genetic background of affective temperaments and its association with depression and suicide: a pilot study

Text of the abstract

Introduction: A better understanding of the genetic and neurobiological background of depression is needed for proper treatment, early diagnosis, and possible prevention. Depression is highly heterogenous, and its different clinical manifestations are likely underpinned by divergent neurobiological processes and different genetic variations. One possible solution to disentangle the heterogeneity of the disease is by using intermediate phenotypes. Affective temperaments possess a strong biological background, heritability, and pathoplastic effect.

Aims: We investigated the genetic background of affective temperaments and their effects on depression and suicidal ideation.

Method: As discovery sample we used a general Hungarian population as part of the NewMood (New Molecules in Mood Disorders, Sixth Framework Program of the EU) study and the Budakalasz Health Examination Survey (BHES). 1092 participants were genotyped, and filled out the 110-item TEMPS-A questionnaire. Our target sample consisted of a general population from Manchester as part of the NewMood study, who provided genotype information and information on depression and suicide phenotypes.
After imputation and quality control, GWA-s were performed on each of the five affective temperaments using Plink2, followed by calculation of PRSs using LDPred2. To test for associations between affective temperaments, depression phenotypes and suicidal attempts and ideation, regression models were run.

Results: In the GWAS, for dysthymic temperament, rs73081363 on chromosome 3 survived correction for genome-wide significance (p= 8.96×10−9). In case of the other four temperaments numerous SNPs were suggestively significant, but no SNP survived Bonferroni correction.
PRSs calculated from the dysthymic and irritable temperaments significantly predicted current depressive symptoms. In case of lifetime suicidal attempts, cyclothymic temperament PRS had a significant risk effect.

Conclusion: Overall, we identified one genome-wide significant SNP associated with the dysthymic temperament and several suggestively significant SNPs associated with the other four affective temperaments. Results of our PRS analyses confirm genetic association between affective temperaments, current depressive symptoms and suicide.

The study was funded by NAP2022-I-4/2022, TKP2021-EGA-25. DG was supported by ÚNKP-23-3-II-SE-93.