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

Mol Psychiatry
Authors
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.

Year of Publication
2016
Journal
Mol Psychiatry
Volume
21
Issue
12
Pages
1680-1689
Date Published
2016 Dec
ISSN
1476-5578
DOI
10.1038/mp.2016.164
PubMed ID
27725656
PubMed Central ID
PMC5144575
Links
Grant list
K24 MH094614 / MH / NIMH NIH HHS / United States
K99 MH101367 / MH / NIMH NIH HHS / United States
K23 MH104515 / MH / NIMH NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
R01 HD050735 / HD / NICHD NIH HHS / United States
K01 MH099232 / MH / NIMH NIH HHS / United States
R01 MH101486 / MH / NIMH NIH HHS / United States