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Biol Psychiatry. 2016 Jun 15;79(12):988-96. doi: 10.1016/j.biopsych.2015.06.019. Epub 2015 Jun 27.

The Relationship of Common Risk Variants and Polygenic Risk for Schizophrenia to Sensorimotor Gating.

Author information

1
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York; James J. Peters Veterans Affairs Medical Center, Mental Illness Research Education and Clinical Center, Bronx, New York. Electronic address: panagiotis.roussos@mssm.edu.
2
Department of Psychology University of Crete, Rethymno.
3
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York.
4
Aghios Charalambos Mental Health Centre, Heraklion.
5
Department of Neurology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
6
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; James J. Peters Veterans Affairs Medical Center, Mental Illness Research Education and Clinical Center, Bronx, New York.
7
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks; Center for Psychiatric Neuroscience, Fenstein Institute for Medical Research, Manhasset; Departments of Psychiatry and Molecular Medicine, Hofstra University School of Medicine, Hempstead, New York.
8
Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.

Abstract

BACKGROUND:

Prepulse inhibition (PPI) of the startle reflex has been suggested as a candidate endophenotype for schizophrenia research, as it shows high heritability and has been found deficient in schizophrenia spectrum disorders. The objectives of the study were to 1) identify common genetic variants associated with baseline startle and PPI; 2) estimate the single nucleotide polymorphism heritability; and 3) examine the relationship of polygenic score for schizophrenia with baseline startle and PPI.

METHODS:

A cohort of healthy young male subjects (n = 1493) originating from the Learning on Genetics of Schizophrenia Spectrum project was assessed for baseline startle and PPI. The most recent genome-wide association study in schizophrenia from the Psychiatric Genomics Consortium 2 was used to calculate polygenic scores.

RESULTS:

Eleven loci showed suggestive association (p < 10(-6)) with baseline startle and PPI in the discovery cohort. Additional genotyping in a replication cohort identified genome-wide significant association at two loci (rs61810702 and rs4718984). These loci were co-localized with expression quantitative trait loci associated with gene expression of nerve growth factor (NGF) and calneuron 1 (CALN1) genes. Estimation of the genetic and environmental contributions to baseline startle and PPI showed a substantial single nucleotide polymorphism heritability for 120-ms PPI stimuli. Increased polygenic risk score for schizophrenia was associated with reduced PPI.

CONCLUSIONS:

Common genetic variation has an important role in the etiology of schizophrenia and PPI impairments. Overall, these data support the idea that PPI is a valid endophenotype that can be used to explore the genetic architecture of schizophrenia.

KEYWORDS:

Baseline startle; Endophenotypes; GWAS; Heritability; Prepulse inhibition; eQTL

PMID:
26212897
DOI:
10.1016/j.biopsych.2015.06.019
[Indexed for MEDLINE]

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