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Cited by 122Epigenetics and DNA MethylationNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

Association Between Promoter Methylation of Serotonin Transporter Gene and Depressive Symptoms: A Monozygotic Twin Study

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Zhao, Jinying, Goldberg, Jack, Bremner, James D., Vaccarino, Viola·2013·Psychosomatic Medicine
DOI 10.1097/psy.0b013e3182924cf4PMC PMC3848698
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Abstract

OBJECTIVE: Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs. METHODS: DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value). RESULTS: Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9-7.9, p = .01). CONCLUSIONS: This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association.

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  • Candidate gene studies suggest increased SLC6A4 methylation in depression and bipolar disorder.

    “with candidate genes studies suggesting an increased in methylation in depression (Kang et al., 2013; Philibert et al., 2008; Zhao, Goldberg, Bremner, & Vaccarino, 2013), BD (Sugawara et al., 2011)”

    From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Zhao, Goldberg, Bremner, & Vaccarino, 2013

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Authors
Zhao, J., Goldberg, J., Bremner, J. D., & Vaccarino, V.
Affiliations
Tulane University (US)
Corresponding author
Zhao, Jinying
ORCID
Venue
Psychosomatic Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-07
Volume
75
Issue
6
Pages
523-529
ISSN
0033-3174 (ISSN-L)
DOI
10.1097/psy.0b013e3182924cf4
PMC
PMC3848698
OpenAlex
W2072289007
Cited by
122
References
48
Citations by year
2025: 7 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 7 · 2017: 12 · 2016: 14 · 2015: 19 · 2014: 18 · 2013: 1
FWCI
7.77
Type
journal article
Language
en
Open access
Locations
  • Psychosomatic Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (K01AG034259, R01AG026255)
  • National Heart, Lung, and Blood Institute (R01HL068630, R21HL092363, K24HL077506, R01HL088726, R01 HL68630)
  • National Institute of Mental Health (R01MH056120, K24MH076955)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091369)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
serotonin transporter, serotonin transporter gene, promoter methylation, DNA methylation, depressive symptoms, depression, monozygotic twins, epigenetics, 5-HTTLPR, CpG sites
MeSH terms
Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Male, Middle Aged, Promoter Regions, Genetic, Stress Disorders, Post-Traumatic, Twins, Monozygotic, Veterans, Linear Models, CpG Islands, DNA Methylation, Epigenesis, Genetic, Serotonin Plasma Membrane Transport Proteins

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