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Affective temperament polygenic risk scores predict depression: investigating the role of environmental factors
- D. Győrik, D. Torok, B. Erdelyi-Hamza, Z. Gal, N. Eszlari, G. Bagdy, G. Juhasz, X. Gonda
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S348
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Introduction
Depressive disorders are known heterogeneous both in their clinical manifestations and etiopathophysiology. Affective temperaments have a strong biological background and heritability, manifest at early age and remain stable throughout the life span, and have a pathoplastic effect in depression. Thus, they have been suggested as intermediate phenotypes for depression.
ObjectivesOur aim was to investigate if polygenic risk scores (PRS) calculated for the five affective temperaments predict depression and to examine their interaction effects of early and recent stressors.
Methods1820 nonrelated participants from a general population were genotyped and provided data on current depression (Brief Symptom Inventory-BSI), early (Childhood Trauma Questionnaire, CHA) and recent stressors (List of Threatening Life Events, RLE), and affective temperaments (Temperament Evaluation of Memphis, Pisa, Paris and San Diego, TEMPS-A). Our previously performed TEMPS-A GWAS analysis was used as discovery sample and the NewMood database as target sample for analysing the effects of affective temperament PRS on depression. Linear regression models were used to calculate the interaction effect of early and recent stressors.
ResultsPRSs derived from anxious, cyclothymic, depressive, and irritable temperaments had a significant effect on current depression, explaining 2.6-7.1% of variance. PRSs calculated from the anxious, depressive and hyperthymic temperaments significantly predicted current depression in interaction with CHA, explaining 10% of variance. In case of interaction models including both early and recent stressors, a significant effect of depressive PRS was found. Detailed results are shown in Table 1.
anxious cyclothymic depressive hyperthymic irritable on BSI-depression R2 .0033 .0071 .0032 .0016 .0026 p-value .011 .0002 .011 .076 .022 in interaction with CHA R2 .1062 .1037 .1029 .1015 .1022 p-value .008 .551 .027 .038 .531 in interaction with RLE R2 .0365 .0402 .0362 .0369 .0368 p-value .396 .140 .483 .227 .480 in interaction with CHA and RLE R2 .1387 .1384 .1395 .1344 .1348 p-value .101 .400 .0009 .981 .930 ConclusionsOur results confirm the genetic association between affective temperaments and depressive symptoms, which highlight their role as possible clinically relevant intermediate phenotypes for depression.
Disclosure of InterestNone Declared
“… wise, amazed, temp’rate, and furious, Loyal and neutral, in a moment”: first heritability analysis of affective temperaments reports remarkably high SNP-based heritability
- X. Gonda, D. Torok, N. Eszlari, D. Gyorik, A. Millinghoffer, G. Bagdy, G. Juhasz
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S352-S353
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- Article
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- You have access Access
- Open access
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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 heritability of depression in GWAS-s is around 8-9%. Heterogeneity of the depressive phenotype may contribute not only to the lack of understanding its genetic background but may also hinder the identification of novel targets. Thus clinically relevant intermediate endophenotypes are needed for. The affective temperaments in the Akiskal model may be considered high-risk states or subclinical manifestations of mood disorders. Considering their strong genetic and biological background, high heritability in family studies, and their temporal stability, they may prove to be relevant endophenotypes for depression.
ObjectivesThe aim of the current study was to investigate the genetic determinants and heritability of affective temperaments based on a GWAS approach.
Methods775 subjects aged between 18-60 years recruited in Budapest, Hungary provided genetic samples and completed questionnaires including the TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego) scale. A genome-wide association analysis was performed with the five affective temperaments as outcome variables. Age, gender, the top 10 principal components of the genome, and the other 4 phenotype were added in the model as covariates. Summary statistics derived from the GWAS analyses were used to estimate the heritability, i.e. the genetic variance explained by the different affective temperaments. LD score regression using LDPred2 [4] was performed to estimate heritability from the beta values and effect size in case of all 5 affective temperament phenotypes.
Resultsrs3798978 showed a genome-wide significance (p=4.44x10-8) for anxious temperament, and several other variants showed suggestive significances for all five temperaments. The highest estimated heritability (h2 = 0.5224) was observed for the depressive temperament, and similarly high heritability was observed for the hyperthymic temperament (h2 = 0.4956). Anxious and cyclothymic temperaments showed almost the same heritability (cyclothymic h2 = 0.1651, anxious h2 = 0.1663), whereas for the irritable temperament, we got negative heritability estimation (h2 = -0.0567), which means that all of the phenotypic variance is explained by environmental factors.
ConclusionsOur analyses yielded remarkably high heritability values for depressive and hyperthymic temperaments explaining 52% and 50% of phenotypic variances. In contrast to the 8-9% SNP-based heritability in depression studies our findings suggest that these temperaments may be relevant endophenotypes for mood disorders.
Disclosure of InterestNone Declared