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Genome-wide Association Analysis Identifies Common Variants Influencing Infant Brain Volumes

Institution:
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
Publisher:
Nature Publishing Group
Publication Date:
Aug-2017
Journal:
Transl Psychiatry
Volume Number:
7
Issue Number:
8
Pages:
e1188
Citation:
Transl Psychiatry. 2017 Aug 1;7(8):e1188.
PubMed ID:
28763065
PMCID:
PMC5611727
Appears in Collections:
NA-MIC
Sponsors:
P50 MH064065/MH/NIMH NIH HHS/United States
R01 MH070890/MH/NIMH NIH HHS/United States
R01 HD053000/HD/NICHD NIH HHS/United States
K01 MH083045/MH/NIMH NIH HHS/United States
UL1 RR025747/RR/NCRR NIH HHS/United States
R01 MH086633/MH/NIMH NIH HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
T32 NS007431/NS/NINDS NIH HHS/United States
U54 EB020403/EB/NIBIB NIH HHS/United States
RC2 MH089983/MH/NIMH NIH HHS/United States
Generated Citation:
Xia K., Zhang J., Ahn M., Jha S., Crowley J.J., Szatkiewicz J., Li T., Zou F., Zhu H., Hibar D., Thompson P., Sullivan P.F., Styner M.A., Gilmore J.H., Knickmeyer R.C. Genome-wide Association Analysis Identifies Common Variants Influencing Infant Brain Volumes. Transl Psychiatry. 2017 Aug 1;7(8):e1188. PMID: 28763065. PMCID: PMC5611727.
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Genome-wide association studies (GWAS) of adolescents and adults are transforming our understanding of how genetic variants impact brain structure and psychiatric risk, but cannot address the reality that psychiatric disorders are unfolding developmental processes with origins in fetal life. To investigate how genetic variation impacts prenatal brain development, we conducted a GWAS of global brain tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume (P=4.15 × 10(-10)). An intronic SNP in WWOX (rs10514437) neared genome-wide significance for white matter volume (P=1.56 × 10(-8)). Additional loci with small P-values included psychiatric GWAS associations and transcription factors expressed in developing brain. Genetic predisposition scores for schizophrenia and ASD, and the number of genes impacted by rare copy number variants (CNV burden) did not predict global brain tissue volumes. Integration of these results with large-scale neuroimaging GWAS in adolescents (PNC) and adults (ENIGMA2) suggests minimal overlap between common variants impacting brain volumes at different ages. Ultimately, by identifying genes contributing to adverse developmental phenotypes, it may be possible to adjust adverse trajectories, preventing or ameliorating psychiatric and developmental disorders.

Additional Material
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Xia-TranslPsychiatry2017-fig1.jpg (187.123kB)