Associations Between Neurodevelopmental Genes, Neuroanatomy, and Ultra High Risk Symptoms of Psychosis in 22q11.2 Deletion Syndrome

作者：Thompson Carlie A; Karelis Jason; Middleton Frank A; Gentile Karen; Coman Ioana L; Radoeva Petya D; Mehta Rashi; Fremont Wanda P; Antshel Kevin M; Faraone Stephen V; Kates Wendy R^*

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2017, 174(3): 295-314.

DOI：10.1002/ajmg.b.32515

• velo-cardio-facial syndrome
• RTN4R
• axonal development
• Freesurfer
• schizophrenia

22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain.

• 出版日期2017-4