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Transl Psychiatry. 2019 Sep 2;9(1):214. doi: 10.1038/s41398-019-0548-9.

Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.

Starnawska A1,2,3, Tan Q4,5, Soerensen M4,5,6, McGue M4,7, Mors O8,9, Børglum AD10,8,11, Christensen K4,5,6,12, Nyegaard M10,8,11, Christiansen L4,6,13.

Author information

1
Department of Biomedicine, Aarhus University, Aarhus, Denmark. as@biomed.au.dk.
2
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. as@biomed.au.dk.
3
Center for Integrative Sequencing, iSEQ, Aarhus Genome Centre, Aarhus University, Aarhus, Denmark. as@biomed.au.dk.
4
The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
5
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
6
The Danish Aging Research Center, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
7
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
8
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
9
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
10
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
11
Center for Integrative Sequencing, iSEQ, Aarhus Genome Centre, Aarhus University, Aarhus, Denmark.
12
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
13
Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Abstract

Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual's quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value = 4.7 × 10-7) and DAZ associated protein 2 (DAZAP2, p-value = 3.13 × 10-8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value = 5.16 × 10-6), SLC29A2 (p-value = 6.15 × 10-6) and AKT1 (p-value = 4.47 × 10-6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.

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