Department of Economics and Business Economics

Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome. / Starnawska, A; Hansen, C S; Sparsø, T; Mazin, W; Olsen, L; Bertalan, M; Buil, A; Bybjerg-Grauholm, J; Bækvad-Hansen, M; Hougaard, D M; Mortensen, P B; Pedersen, C B; Nyegaard, M; Werge, T; Weinsheimer, S.

In: Translational Psychiatry, Vol. 7, No. 8, 1221, 29.08.2017, p. e1221.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Starnawska, A, Hansen, CS, Sparsø, T, Mazin, W, Olsen, L, Bertalan, M, Buil, A, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Hougaard, DM, Mortensen, PB, Pedersen, CB, Nyegaard, M, Werge, T & Weinsheimer, S 2017, 'Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome', Translational Psychiatry, vol. 7, no. 8, 1221, pp. e1221. https://doi.org/10.1038/tp.2017.181

APA

Starnawska, A., Hansen, C. S., Sparsø, T., Mazin, W., Olsen, L., Bertalan, M., ... Weinsheimer, S. (2017). Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome. Translational Psychiatry, 7(8), e1221. [1221]. https://doi.org/10.1038/tp.2017.181

CBE

Starnawska A, Hansen CS, Sparsø T, Mazin W, Olsen L, Bertalan M, Buil A, Bybjerg-Grauholm J, Bækvad-Hansen M, Hougaard DM, Mortensen PB, Pedersen CB, Nyegaard M, Werge T, Weinsheimer S. 2017. Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome. Translational Psychiatry. 7(8):e1221. https://doi.org/10.1038/tp.2017.181

MLA

Vancouver

Starnawska A, Hansen CS, Sparsø T, Mazin W, Olsen L, Bertalan M et al. Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome. Translational Psychiatry. 2017 Aug 29;7(8):e1221. 1221. https://doi.org/10.1038/tp.2017.181

Author

Starnawska, A ; Hansen, C S ; Sparsø, T ; Mazin, W ; Olsen, L ; Bertalan, M ; Buil, A ; Bybjerg-Grauholm, J ; Bækvad-Hansen, M ; Hougaard, D M ; Mortensen, P B ; Pedersen, C B ; Nyegaard, M ; Werge, T ; Weinsheimer, S. / Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome. In: Translational Psychiatry. 2017 ; Vol. 7, No. 8. pp. e1221.

Bibtex

@article{e25c8ccacdf649d6977e4a4412a27d59,
title = "Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome",
abstract = "Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate with mental disorder later in life. DNA methylation was measured genome-wide from neonatal dried blood spots in a cohort of 164 individuals with 22q11.2DS, including 48 individuals diagnosed with a psychiatric disorder. Among several CpG sites with P-value<10(-6), we identified cg23546855 (P-value=2.15 × 10(-7)) mapping to STK32C to be associated with a later psychiatric diagnosis. Pathway analysis of the top findings resulted in the identification of several Gene Ontology pathways to be significantly enriched (P-value<0.05 after Benjamini-Hochberg correction); among them are the following: neurogenesis, neuron development, neuron projection development, astrocyte development, axonogenesis and axon guidance. In addition, we identified differentially methylated CpG sites in LRP2BP (P-value=5.37 × 10(-8)) to be associated with intellectual disability (F70-79), in TOP1 (P-value=1.86 × 10(-7)) with behavioral disorders (F90-98), in NOSIP (P-value=5.12 × 10(-8)) with disorders of psychological development (F80-89) and in SEMA4B (P-value=4.02 × 10(-7)) with schizophrenia spectrum disorders (F20-29). In conclusion, our study suggests an association of DNA methylation differences at birth with development of mental disorder later in life in 22q11.2DS individuals.",
keywords = "ADHESION MOLECULE NCAM, BRAIN, CARDIO-FACIAL-SYNDROME, COPY NUMBER VARIATION, EXPRESSION, GENE, PSYCHIATRIC-DISORDERS, SCHIZOPHRENIA, SPECTRUM DISORDERS, WIDE ASSOCIATION",
author = "A Starnawska and Hansen, {C S} and T Spars{\o} and W Mazin and L Olsen and M Bertalan and A Buil and J Bybjerg-Grauholm and M B{\ae}kvad-Hansen and Hougaard, {D M} and Mortensen, {P B} and Pedersen, {C B} and M Nyegaard and T Werge and S Weinsheimer",
year = "2017",
month = "8",
day = "29",
doi = "10.1038/tp.2017.181",
language = "English",
volume = "7",
pages = "e1221",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Differential DNA methylation at birth associated with mental disorder in individuals with 22q11.2 deletion syndrome

AU - Starnawska, A

AU - Hansen, C S

AU - Sparsø, T

AU - Mazin, W

AU - Olsen, L

AU - Bertalan, M

AU - Buil, A

AU - Bybjerg-Grauholm, J

AU - Bækvad-Hansen, M

AU - Hougaard, D M

AU - Mortensen, P B

AU - Pedersen, C B

AU - Nyegaard, M

AU - Werge, T

AU - Weinsheimer, S

PY - 2017/8/29

Y1 - 2017/8/29

N2 - Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate with mental disorder later in life. DNA methylation was measured genome-wide from neonatal dried blood spots in a cohort of 164 individuals with 22q11.2DS, including 48 individuals diagnosed with a psychiatric disorder. Among several CpG sites with P-value<10(-6), we identified cg23546855 (P-value=2.15 × 10(-7)) mapping to STK32C to be associated with a later psychiatric diagnosis. Pathway analysis of the top findings resulted in the identification of several Gene Ontology pathways to be significantly enriched (P-value<0.05 after Benjamini-Hochberg correction); among them are the following: neurogenesis, neuron development, neuron projection development, astrocyte development, axonogenesis and axon guidance. In addition, we identified differentially methylated CpG sites in LRP2BP (P-value=5.37 × 10(-8)) to be associated with intellectual disability (F70-79), in TOP1 (P-value=1.86 × 10(-7)) with behavioral disorders (F90-98), in NOSIP (P-value=5.12 × 10(-8)) with disorders of psychological development (F80-89) and in SEMA4B (P-value=4.02 × 10(-7)) with schizophrenia spectrum disorders (F20-29). In conclusion, our study suggests an association of DNA methylation differences at birth with development of mental disorder later in life in 22q11.2DS individuals.

AB - Individuals with 22q11.2 deletion syndrome (DS) have an increased risk of comorbid mental disorders including schizophrenia, attention deficit hyperactivity disorder, depression, as well as intellectual disability. Although most 22q11.2 deletion carriers have the long 3-Mb form of the hemizygous deletion, there remains a large variation in the development and progression of psychiatric disorders, which suggests that alternative factors contribute to the pathogenesis. In this study we investigated whether neonatal DNA methylation signatures in individuals with the 22q11.2 deletion associate with mental disorder later in life. DNA methylation was measured genome-wide from neonatal dried blood spots in a cohort of 164 individuals with 22q11.2DS, including 48 individuals diagnosed with a psychiatric disorder. Among several CpG sites with P-value<10(-6), we identified cg23546855 (P-value=2.15 × 10(-7)) mapping to STK32C to be associated with a later psychiatric diagnosis. Pathway analysis of the top findings resulted in the identification of several Gene Ontology pathways to be significantly enriched (P-value<0.05 after Benjamini-Hochberg correction); among them are the following: neurogenesis, neuron development, neuron projection development, astrocyte development, axonogenesis and axon guidance. In addition, we identified differentially methylated CpG sites in LRP2BP (P-value=5.37 × 10(-8)) to be associated with intellectual disability (F70-79), in TOP1 (P-value=1.86 × 10(-7)) with behavioral disorders (F90-98), in NOSIP (P-value=5.12 × 10(-8)) with disorders of psychological development (F80-89) and in SEMA4B (P-value=4.02 × 10(-7)) with schizophrenia spectrum disorders (F20-29). In conclusion, our study suggests an association of DNA methylation differences at birth with development of mental disorder later in life in 22q11.2DS individuals.

KW - ADHESION MOLECULE NCAM

KW - BRAIN

KW - CARDIO-FACIAL-SYNDROME

KW - COPY NUMBER VARIATION

KW - EXPRESSION

KW - GENE

KW - PSYCHIATRIC-DISORDERS

KW - SCHIZOPHRENIA

KW - SPECTRUM DISORDERS

KW - WIDE ASSOCIATION

U2 - 10.1038/tp.2017.181

DO - 10.1038/tp.2017.181

M3 - Journal article

VL - 7

SP - e1221

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 8

M1 - 1221

ER -