TY - JOUR
T1 - Common variants in psychiatric risk genes predict brain structure at birth
AU - Knickmeyer, Rebecca C.
AU - Wang, Jiaping
AU - Zhu, Hongtu
AU - Geng, Xiujuan
AU - Woolson, Sandra
AU - Hamer, Robert M.
AU - Konneker, Thomas
AU - Lin, Weili
AU - Styner, Martin
AU - Gilmore, John H.
N1 - Funding Information:
This work was supported by the National Institutes of Health (MH064065 and MH070890 to J.H.G., MH083045 and MH092335 to R.C.K., HD03110 and MH091645 to M.S., and RR025747, P01CA142538, MH086633, EB005149, and AG033387 to H.Z.).
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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.
AB - 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.
KW - catechol-O-methyltransferase
KW - cortex
KW - disrupted-in-schizophrenia-1
KW - neonate
KW - neuroimaging
UR - http://www.scopus.com/inward/record.url?scp=84898870011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898870011&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhs401
DO - 10.1093/cercor/bhs401
M3 - Article
C2 - 23283688
AN - SCOPUS:84898870011
SN - 1047-3211
VL - 24
SP - 1230
EP - 1246
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 5
ER -