title: Common variants in psychiatric risk genes predict brain structure at birth.
abstract: Studies in adolescents and adults have demonstrated that polymorphisms in putative psychiatric risk genes are associated with differences in brain structure, but cannot address when in development these relationships arise. To determine if common genetic variants in disrupted-in-schizophrenia-1 (DISC1; rs821616 and rs6675281), catechol-O-methyltransferase (COMT; rs4680), neuregulin 1 (NRG1; rs35753505 and rs6994992), apolipoprotein E (APOE; ε3ε4 vs. ε3ε3), estrogen receptor alpha (ESR1; rs9340799 and rs2234693), brain-derived neurotrophic factor (BDNF; rs6265), and glutamate decarboxylase 1 (GAD1; rs2270335) are associated with individual differences in brain tissue volumes in neonates, we applied both automated region-of-interest volumetry and tensor-based morphometry to a sample of 272 neonates who had received high-resolution magnetic resonance imaging scans. ESR1 (rs9340799) predicted intracranial volume. Local variation in gray matter (GM) volume was significantly associated with polymorphisms in DISC1 (rs821616), COMT, NRG1, APOE, ESR1 (rs9340799), and BDNF. No associations were identified for DISC1 (rs6675281), ESR1 (rs2234693), or GAD1. Of note, neonates homozygous for the DISC1 (rs821616) serine allele exhibited numerous large clusters of reduced GM in the frontal lobes, and neonates homozygous for the COMT valine allele exhibited reduced GM in the temporal cortex and hippocampus, mirroring findings in adults. The results highlight the importance of prenatal brain development in mediating psychiatric risk.
authors.affiliation: Department of Psychiatry.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Knickmeyer
authors.forename: Jiaping
authors.initials: J
authors.lastname: Wang
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Geng
authors.forename: Sandra
authors.initials: S
authors.lastname: Woolson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hamer
authors.forename: Thomas
authors.initials: T
authors.lastname: Konneker
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.forename: John H
authors.initials: JH
authors.lastname: Gilmore
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000254:growth & development* / Q000473:pathology*; D001931:Brain Mapping; D016241:Child of Impaired Parents; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D011247:Pregnancy; D055815:Young Adult
chemical_list: D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: catechol-O-methyltransferase; cortex; disrupted-in-schizophrenia-1; neonate; neuroimaging