title: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes.
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.
authors: Singapore Institute for Clinical Sciences.
authors: Li
authors: L
authors: Chen
authors: Singapore Institute for Clinical Sciences.
authors: Hong
authors: H
authors: Pan
authors: National University of Singapore.
authors: Ta Anh
authors: TA
authors: Tuan
authors: Singapore Institute for Clinical Sciences.
authors: Ai Ling
authors: AL
authors: Teh
authors: University of British Columbia.
authors: Julia L
authors: JL
authors: MacIsaac
authors: University of British Columbia.
authors: Sarah M
authors: SM
authors: Mah
authors: University of British Columbia.
authors: Lisa M
authors: LM
authors: McEwen
authors: National University of Singapore.
authors: Yue
authors: Y
authors: Li
authors: KK Women's and Children's Hospital,Singapore.
authors: Helen
authors: H
authors: Chen
authors: Singapore Institute for Clinical Sciences.
authors: Birit F P
authors: BF
authors: Broekman
authors: Singapore Institute for Clinical Sciences.
authors: Jan Paul
authors: JP
authors: Buschdorf
authors: Singapore Institute for Clinical Sciences.
authors: Yap Seng
authors: YS
authors: Chong
authors: KK Women's and Children's Hospital,Singapore.
authors: Kenneth
authors: K
authors: Kwek
authors: National University of Singapore.
authors: Seang Mei
authors: SM
authors: Saw
authors: Singapore Institute for Clinical Sciences.
authors: Peter D
authors: PD
authors: Gluckman
authors: KK Women's and Children's Hospital,Singapore.
authors: Marielle V
authors: MV
authors: Fortier
authors: Singapore Institute for Clinical Sciences.
authors: Anne
authors: A
authors: Rifkin-Graboi
authors: University of British Columbia.
authors: Michael S
authors: MS
authors: Kobor
authors: Singapore Institute for Clinical Sciences.
authors: Anqi
authors: A
authors: Qiu
authors: Singapore Institute for Clinical Sciences.
authors: Michael J
authors: MJ
authors: Meaney
authors: Singapore Institute for Clinical Sciences.
authors: Joanna D
authors: JD
authors: Holbrook
mesh_terms: D000328:Adult; D000679:Amygdala / Q000033:anatomy & histology* / Q000473:pathology; D001007:Anxiety / Q000150:complications / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006624:Hippocampus / Q000033:anatomy & histology* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012846:Singapore
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human