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Common Variants in Psychiatric Risk Genes Predict Brain Structure at Birth

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Publication Date:
Cereb Cortex
Volume Number:
Issue Number:
Cereb Cortex. 2014 May;24(5):1230-46.
PubMed ID:
catechol-O-methyltransferase, cortex, disrupted-in-schizophrenia-1, neonate, neuroimaging
Appears in Collections:
K01 MH083045/MH/NIMH NIH HHS/United States
P01 CA142538/CA/NCI NIH HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
P50 MH064065/MH/NIMH NIH HHS/United States
R01 MH070890/MH/NIMH NIH HHS/United States
R01 MH086633/MH/NIMH NIH HHS/United States
R01 MH091645/MH/NIMH NIH HHS/United States
R01 MH092335/MH/NIMH NIH HHS/United States
R21 AG033387/AG/NIA NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
UL1 RR025747/RR/NCRR NIH HHS/United States
Generated Citation:
Knickmeyer R.C., Wang J., Zhu H., Geng X., Woolson S., Hamer R.M., Konneker T., Lin W., Styner M., Gilmore J.H. Common Variants in Psychiatric Risk Genes Predict Brain Structure at Birth. Cereb Cortex. 2014 May;24(5):1230-46. PMID: 23283688. PMCID: PMC3977618.
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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.

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