Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia

Lee, P. H., Baker, J. T., Holmes, A. J., Jahanshad, N., Ge, T., Jung, J. -Y., Cruz, Y., Manoach, D. S., Hibar, D. P., Faskowitz, J., McMahon, K. L., De Zubicaray, G. I., Martin, N. H., Wright, M. J., Ongur, D., Buckner, R., Roffman, J., Thompson, P. M. and Smoller, J. W. (2016) Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia. Molecular Psychiatry, 21 12: 1680-1689. doi:10.1038/mp.2016.164

Author Lee, P. H.
Baker, J. T.
Holmes, A. J.
Jahanshad, N.
Ge, T.
Jung, J. -Y.
Cruz, Y.
Manoach, D. S.
Hibar, D. P.
Faskowitz, J.
McMahon, K. L.
De Zubicaray, G. I.
Martin, N. H.
Wright, M. J.
Ongur, D.
Buckner, R.
Roffman, J.
Thompson, P. M.
Smoller, J. W.
Title Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2016-12-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/mp.2016.164
Open Access Status Not yet assessed
Volume 21
Issue 12
Start page 1680
End page 1689
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
Abstract Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.
Keyword Biochemistry & Molecular Biology
Biochemistry & Molecular Biology
Neurosciences & Neurology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID K24 MH094614
K99 MH101367
K23 MH104515
U54 EB020403
R01 HD050735
K01 MH099232
R01 MH101486
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
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