PhD Scientific Days 2023

Budapest, 22-23 June 2023

Mental Health Sciences - Posters M

CLOCK gene plays role in the genetic background of depression after stressful life events – a GWAS study

Berta Erdelyi-Hamza1, Dora Torok2, Zsofia Gal2, Dorka Gyorik2,3, Nora Eszlari2,4, Gyorgy Bagdy2,4, Gabriella Juhasz2,5, Xenia Gonda1,2

1 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
2 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary
3 Faculty of Medicine, Semmelweis University, Budapest, Hungary
4 NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary
5 SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction Several factors, including biological and environmental contributors and gene-environment interactions are involved in the background of depression. This affective disorder is highly heterogeneous in both its manifestations and etiopathology, divergent eurobiological pathways, and thus different genes may play a role in its development following major stress exposure. In the present study we investigate the genetic background of current reactive depressive states after stressful life events with a genome-wide association study (GWAS).

Methods GWAS was conducted in the UK Biobank database. We included subjects who reported
several severe stressful life events in the past two years (N=37 218). Depressive symptoms occurring in the past two weeks were measured using the Current Depression Score. SNP-level association was assessed using linear regression models, assuming additive genetic effects using PLINK2.0, with sex, age and the first ten principal components (PC) of the genetic data as covariates. Bonferroni-corrected significance threshold was p≤5.0×10-8 , suggestive significance threshold was p≤1.0×10-5. Results were interpreted using FUMA v1.3.8.

Results No SNPs with genome-wide significance were found. Six SNPs showed suggestive significance (rs979882: β=0.0875282, P=9.36746E-06; rs35034096: β=0.0885559, P=5.39273E-06; rs7014345: β=-0.0899653, P=3.35005E-06; rs12039750: β=0.141137, P=3.16919E-06; rs72642583: β=-0.220299, P=7.41319E-07; rs138310410: β=0.393902, P=2.37154E-07). The lead SNP rs138310410 with highest significance is located near the CLOCK gene.

Conclusions: Our results support involvement of the CLOCK (Circadian Locomotor Output Cycles Kaput) gene, a major activator of downstream elements of a pathway involved in the generation of circadian rhythm, in depression following stress exposure. This gene has previously been implicated both in depression and in mediating the effects of stress in the development of various somatic and psychiatric disorders. Divergent pathophysiological processes occurring as a consequence of stress may lead to depression, and understanding them may provide important aspects for identifying targets for the treatment of reactive depression.

Supported by: 2017-1.2.1-NKP-2017-00002; 2019-2.1.7-ERA-NET-2020-00005; 2020-4.1.1.-TKP2020;
TKP2021-EGA-25, summary statistic data is provided by 23andMe.
DG was supported from NTP-NFTÖ-21-B-0096 of the New National Excellence Program of the Ministry
of Human Capacities and from EFOP-3.6.3-VEKOP-16-2017-00009.

University: Semmelweis University, Budapest
Doctoral School: Mental Health Sciences, Psychiatry Program