DNA methylation of the KLK8 gene in depression symptomatology

Anna Starnawska; Lina Bukowski; Ana Chernomorchenko; Betina Elfving; Heidi Kaastrup Müller; Edwin van den Oord; Karolina Aberg; Jerry Guintivano; Jakob Grove; Ole Mors; Anders D Børglum; Anders L Nielsen; Per Qvist; Nicklas Heine Staunstrup

doi:10.1186/s13148-021-01184-5

DNA methylation of the KLK8 gene in depression symptomatology

Anna Starnawska, Lina Bukowski, Ana Chernomorchenko, Betina Elfving, Heidi Kaastrup Müller, Edwin van den Oord, Karolina Aberg, Jerry Guintivano, Jakob Grove, Ole Mors, Anders D Børglum, Anders L Nielsen, Per Qvist, Nicklas Heine Staunstrup

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background: Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. Methods: In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. Results: DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for ‘Depressed mood,’ and for CpG2 = 0.03 for ‘Loss of self-confidence with other people’). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Conclusions: Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis.

Original language	English
Article number	200
Journal	Clinical Epigenetics
Volume	13
Issue	1
ISSN	1868-7075
DOIs	https://doi.org/10.1186/s13148-021-01184-5
Publication status	Published - 29 Oct 2021

Keywords

DNA methylation
Depression
Epigenetics
KLK8
Neuropsin

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10.1186/s13148-021-01184-5

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title = "DNA methylation of the KLK8 gene in depression symptomatology",

abstract = "Background: Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. Methods: In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. Results: DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for {\textquoteleft}Depressed mood,{\textquoteright} and for CpG2 = 0.03 for {\textquoteleft}Loss of self-confidence with other people{\textquoteright}). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Conclusions: Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis.",

keywords = "DNA methylation, Depression, Epigenetics, KLK8, Neuropsin",

author = "Anna Starnawska and Lina Bukowski and Ana Chernomorchenko and Betina Elfving and M{\"u}ller, {Heidi Kaastrup} and {van den Oord}, Edwin and Karolina Aberg and Jerry Guintivano and Jakob Grove and Ole Mors and B{\o}rglum, {Anders D} and Nielsen, {Anders L} and Per Qvist and Staunstrup, {Nicklas Heine}",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

month = oct,

day = "29",

doi = "10.1186/s13148-021-01184-5",

language = "English",

volume = "13",

journal = "Clinical Epigenetics",

issn = "1868-7075",

publisher = "BioMed Central Ltd.",

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TY - JOUR

T1 - DNA methylation of the KLK8 gene in depression symptomatology

AU - Starnawska, Anna

AU - Bukowski, Lina

AU - Chernomorchenko, Ana

AU - Elfving, Betina

AU - Müller, Heidi Kaastrup

AU - van den Oord, Edwin

AU - Aberg, Karolina

AU - Guintivano, Jerry

AU - Grove, Jakob

AU - Mors, Ole

AU - Børglum, Anders D

AU - Nielsen, Anders L

AU - Qvist, Per

AU - Staunstrup, Nicklas Heine

PY - 2021/10/29

Y1 - 2021/10/29

N2 - Background: Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. Methods: In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. Results: DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for ‘Depressed mood,’ and for CpG2 = 0.03 for ‘Loss of self-confidence with other people’). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Conclusions: Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis.

AB - Background: Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. Methods: In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. Results: DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for ‘Depressed mood,’ and for CpG2 = 0.03 for ‘Loss of self-confidence with other people’). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Conclusions: Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis.

KW - DNA methylation

KW - Depression

KW - Epigenetics

KW - KLK8

KW - Neuropsin

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U2 - 10.1186/s13148-021-01184-5

DO - 10.1186/s13148-021-01184-5

M3 - Journal article

C2 - 34715912

SN - 1868-7075

VL - 13

JO - Clinical Epigenetics

JF - Clinical Epigenetics

IS - 1

M1 - 200

ER -

DNA methylation of the KLK8 gene in depression symptomatology

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Keywords

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