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Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

journal contribution
posted on 2023-06-08, 19:48 authored by P T Goodbourn, Jenny BostenJenny Bosten, G Bargary, R E Hogg, A J Lawrance-Owen, J D Mollon
Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642?758 single nucleotide polymorphism (SNP) markers. A significant association (P?=?7.9?×?10(-9) ) was found with the SNP marker rs1797052, situated in the 5'-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the a?=?0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements.

History

Publication status

  • Published

File Version

  • Published version

Journal

Genes, Brain and Behavior

ISSN

1601-1848

Publisher

Blackwell Publishing

Issue

2

Volume

13

Page range

144-151

Department affiliated with

  • Psychology Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2015-01-28

First Compliant Deposit (FCD) Date

2015-01-28

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