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Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes

Published online by Cambridge University Press:  02 February 2015

Li Chen ,
Hong Pan ,
Ta Anh Tuan ,
Ai Ling Teh ,
Julia L. MacIsaac ,
Sarah M. Mah ,
Lisa M. McEwen ,
Yue Li ,
Helen Chen  and
Birit F. P. Broekman
...Show all authors
Li Chen
Affiliation:
Singapore Institute for Clinical Sciences
Hong Pan
Affiliation:
Singapore Institute for Clinical Sciences Nanyang Technological University
Ta Anh Tuan
Affiliation:
National University of Singapore
Ai Ling Teh
Affiliation:
Singapore Institute for Clinical Sciences
Julia L. MacIsaac
Affiliation:
University of British Columbia
Sarah M. Mah
Affiliation:
University of British Columbia
Lisa M. McEwen
Affiliation:
University of British Columbia
Yue Li
Affiliation:
National University of Singapore
Helen Chen
Affiliation:
KK Women's and Children's Hospital, Singapore
Birit F. P. Broekman
Affiliation:
Singapore Institute for Clinical Sciences National University Health System, Singapore
Jan Paul Buschdorf
Affiliation:
Singapore Institute for Clinical Sciences
Yap Seng Chong
Affiliation:
Singapore Institute for Clinical Sciences National University Health System, Singapore
Kenneth Kwek
Affiliation:
KK Women's and Children's Hospital, Singapore Duke–National University of Singapore
Seang Mei Saw
Affiliation:
National University of Singapore National University Health System, Singapore
Peter D. Gluckman
Affiliation:
Singapore Institute for Clinical Sciences University of Auckland
Marielle V. Fortier
Affiliation:
KK Women's and Children's Hospital, Singapore
Anne Rifkin-Graboi
Affiliation:
Singapore Institute for Clinical Sciences
Michael S. Kobor
Affiliation:
University of British Columbia
Anqi Qiu
Affiliation:
Singapore Institute for Clinical Sciences National University of Singapore
Michael J. Meaney*
Affiliation:
Singapore Institute for Clinical Sciences McGill University
Joanna D. Holbrook*
Affiliation:
Singapore Institute for Clinical Sciences
*
Address correspondence and reprint requests to: Joanna D. Holbrook, Singapore Institute for Clinical Sciences, 30 Medical Drive, Singapore 116709; E-mail: [email protected]; and/or Michael J. Meaney, Ludmer Centre for Neuroinformatics & Mental Health, Douglas University Mental Health Research Institute, McGill University, 6875 LaSalle, Montreal, Quebec, H4H1R3, Canada; E-mail: [email protected].
Address correspondence and reprint requests to: Joanna D. Holbrook, Singapore Institute for Clinical Sciences, 30 Medical Drive, Singapore 116709; E-mail: [email protected]; and/or Michael J. Meaney, Ludmer Centre for Neuroinformatics & Mental Health, Douglas University Mental Health Research Institute, McGill University, 6875 LaSalle, Montreal, Quebec, H4H1R3, Canada; E-mail: [email protected].
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Abstract

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Type
Special Section Articles
Information
Development and Psychopathology , Volume 27 , Issue 1: What Works for Whom? Genetic Moderation of Intervention Efficacy , February 2015 , pp. 137 - 150
Copyright
Copyright © Cambridge University Press 2015 

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