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

A. Starnawska, Q. Tan, M. Soerensen, M. McGue, O. Mors, A. D. Børglum, K. Christensen, M. Nyegaard, L. Christiansen

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number214
JournalTranslational psychiatry
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Monozygotic Twins
Depression
DNA Methylation
Epigenomics
Genes
Genetic Promoter Regions
Mental Disorders
Blood Cells
Flow Cytometry
Quality of Life
Genome

Cite this

Starnawska, A., Tan, Q., Soerensen, M., McGue, M., Mors, O., Børglum, A. D., ... Christiansen, L. (2019). Epigenome-wide association study of depression symptomatology in elderly monozygotic twins. Translational psychiatry, 9(1), [214]. https://doi.org/10.1038/s41398-019-0548-9

Epigenome-wide association study of depression symptomatology in elderly monozygotic twins. / Starnawska, A.; Tan, Q.; Soerensen, M.; McGue, M.; Mors, O.; Børglum, A. D.; Christensen, K.; Nyegaard, M.; Christiansen, L.

In: Translational psychiatry, Vol. 9, No. 1, 214, 01.12.2019.

Research output: Contribution to journalArticle

Starnawska, A, Tan, Q, Soerensen, M, McGue, M, Mors, O, Børglum, AD, Christensen, K, Nyegaard, M & Christiansen, L 2019, 'Epigenome-wide association study of depression symptomatology in elderly monozygotic twins', Translational psychiatry, vol. 9, no. 1, 214. https://doi.org/10.1038/s41398-019-0548-9
Starnawska, A. ; Tan, Q. ; Soerensen, M. ; McGue, M. ; Mors, O. ; Børglum, A. D. ; Christensen, K. ; Nyegaard, M. ; Christiansen, L. / Epigenome-wide association study of depression symptomatology in elderly monozygotic twins. In: Translational psychiatry. 2019 ; Vol. 9, No. 1.
@article{041f05d7f4e344e5b8b4108075bf0854,
title = "Epigenome-wide association study of depression symptomatology in elderly monozygotic twins",
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.",
author = "A. Starnawska and Q. Tan and M. Soerensen and M. McGue and O. Mors and B{\o}rglum, {A. D.} and K. Christensen and M. Nyegaard and L. Christiansen",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41398-019-0548-9",
language = "English (US)",
volume = "9",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Epigenome-wide association study of depression symptomatology in elderly monozygotic twins

AU - Starnawska, A.

AU - Tan, Q.

AU - Soerensen, M.

AU - McGue, M.

AU - Mors, O.

AU - Børglum, A. D.

AU - Christensen, K.

AU - Nyegaard, M.

AU - Christiansen, L.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071778058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071778058&partnerID=8YFLogxK

U2 - 10.1038/s41398-019-0548-9

DO - 10.1038/s41398-019-0548-9

M3 - Article

C2 - 31477683

AN - SCOPUS:85071778058

VL - 9

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 214

ER -