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- Title
Mapping 22ql 1.2 Gene Dosage Effects on Brain Morphometry.
- Authors
Lin, Amy; Ching, Christopher R. K.; Vajdi, Ariana; Daqiang Sun; Jonas, Rachel K.; Jalbrzikowski, Maria; Kushan-Wells, Leila; Hansen, Laura Pacheco; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M.; Bearden, Carrie E.
- Abstract
Reciprocal chromosomal rearrangements at the 22ql 1.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q 11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22ql 1.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22ql 1.2 deletions (22q-del; 32 males), 21 with 22ql 1.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22ql 1.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control < duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22ql 1.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development.
- Subjects
GENE mapping; CHROMOSOMAL rearrangement; LOCUS (Genetics); BRAIN diseases; GENETICS of schizophrenia; AMYGDALOID body; DISEASE risk factors
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 26, p6183
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3759-16.2017