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

Anna Starnawska, Qihua Tan, Mette Sørensen, Matt McGue, Ole Mors, Anders Dupont Børglum, Kaare Christensen, Mette Nyegaard, Lene Christiansen

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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
Article number214
JournalTranslational Psychiatry
Volume9
Issue number1
Number of pages14
ISSN2158-3188
DOIs
Publication statusPublished - 2. Sep 2019

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Monozygotic Twins
Depression
DNA Methylation
Epigenomics
Flow Cytometry
Quality of Life

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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 = "Anna Starnawska and Qihua Tan and Mette S{\o}rensen and Matt McGue and Ole Mors and B{\o}rglum, {Anders Dupont} and Kaare Christensen and Mette Nyegaard and Lene Christiansen",
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language = "English",
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Epigenome-wide association study of depression symptomatology in elderly monozygotic twins. / Starnawska, Anna; Tan, Qihua; Sørensen, Mette; McGue, Matt; Mors, Ole; Børglum, Anders Dupont; Christensen, Kaare; Nyegaard, Mette; Christiansen, Lene.

In: Translational Psychiatry, Vol. 9, No. 1, 214, 02.09.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

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

AU - Starnawska, Anna

AU - Tan, Qihua

AU - Sørensen, Mette

AU - McGue, Matt

AU - Mors, Ole

AU - Børglum, Anders Dupont

AU - Christensen, Kaare

AU - Nyegaard, Mette

AU - Christiansen, Lene

PY - 2019/9/2

Y1 - 2019/9/2

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.

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DO - 10.1038/s41398-019-0548-9

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JO - Translational Psychiatry

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SN - 2158-3188

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