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The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males.
Biol Psychiatry. 2011 Mar 01; 69(5):479-86.BP

Abstract

BACKGROUND

Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function. The objective of this cross-sectional genetic association study was to determine the relationship of six core single-nucleotide polymorphisms within the NRG1 gene identified as promising schizophrenia risk genes (rs6994992, SNP8NRG221132, SNP8NRG241930, rs3924999, rs2439272 and rs10503929) to prepulse inhibition (PPI) of the acoustic startle reflex, a well validated schizophrenia endophenotype.

METHODS

PPI was tested in a highly homogeneous study entry cohort (n = 445) of carefully screened healthy, young male army conscripts originating from the Greek LOGOS project (Learning on Genetics of Schizophrenia Spectrum). The QTPHASE from the UNPHASED package was used for the association analysis of each single-nucleotide polymorphisms or haplotype data.

RESULTS

Reduced PPI, particularly at 75-dB_120-msec and 85-dB_60-msec trials, was related to the SNP8NRG241930 G allele and especially the rs6994992 T allele and rs2439272 C allele. Haplotype analysis followed up by risk versus no-risk groups Analysis of variance confirmed that the rs10503929 and rs3924999 SNPs were also associated with PPI reductions, when combined with rs2439272.

CONCLUSIONS

We provide solid evidence for a role of NRG1 risk genotype variations in PPI reductions in a large and demographically and genetically highly homogeneous cohort of healthy young males. These results further validate NRG1 as a candidate gene for the schizophrenia and spectrum disorders and improve our understanding of its functional mechanisms within the human brain because they suggest an influence of the gene in the neural substrate mediating sensorimotor gating.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Roussos P
Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. roussosp@edu.med.uoc.gr
Giakoumaki SG
No affiliation info available
Adamaki E
No affiliation info available
Bitsios P
No affiliation info available

MeSH

AdolescentAdultDNAElectromyographyGenetic MarkersGenome-Wide Association StudyGenotypeHaplotypesHumansMaleMilitary PersonnelNeuregulin-1Polymorphism, GeneticReflex, StartleRiskSchizophreniaSensory GatingYoung Adult

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21035784

Citation

Roussos, Panos, et al. "The Influence of Schizophrenia-related Neuregulin-1 Polymorphisms On Sensorimotor Gating in Healthy Males." Biological Psychiatry, vol. 69, no. 5, 2011, pp. 479-86.
Roussos P, Giakoumaki SG, Adamaki E, et al. The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males. Biol Psychiatry. 2011;69(5):479-86.
Roussos, P., Giakoumaki, S. G., Adamaki, E., & Bitsios, P. (2011). The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males. Biological Psychiatry, 69(5), 479-86. https://doi.org/10.1016/j.biopsych.2010.09.009
Roussos P, et al. The Influence of Schizophrenia-related Neuregulin-1 Polymorphisms On Sensorimotor Gating in Healthy Males. Biol Psychiatry. 2011 Mar 1;69(5):479-86. PubMed PMID: 21035784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males. AU - Roussos,Panos, AU - Giakoumaki,Stella G, AU - Adamaki,Eva, AU - Bitsios,Panos, Y1 - 2010/10/30/ PY - 2010/06/18/received PY - 2010/08/10/revised PY - 2010/09/06/accepted PY - 2010/11/2/entrez PY - 2010/11/3/pubmed PY - 2011/6/1/medline SP - 479 EP - 86 JF - Biological psychiatry JO - Biol Psychiatry VL - 69 IS - 5 N2 - BACKGROUND: Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function. The objective of this cross-sectional genetic association study was to determine the relationship of six core single-nucleotide polymorphisms within the NRG1 gene identified as promising schizophrenia risk genes (rs6994992, SNP8NRG221132, SNP8NRG241930, rs3924999, rs2439272 and rs10503929) to prepulse inhibition (PPI) of the acoustic startle reflex, a well validated schizophrenia endophenotype. METHODS: PPI was tested in a highly homogeneous study entry cohort (n = 445) of carefully screened healthy, young male army conscripts originating from the Greek LOGOS project (Learning on Genetics of Schizophrenia Spectrum). The QTPHASE from the UNPHASED package was used for the association analysis of each single-nucleotide polymorphisms or haplotype data. RESULTS: Reduced PPI, particularly at 75-dB_120-msec and 85-dB_60-msec trials, was related to the SNP8NRG241930 G allele and especially the rs6994992 T allele and rs2439272 C allele. Haplotype analysis followed up by risk versus no-risk groups Analysis of variance confirmed that the rs10503929 and rs3924999 SNPs were also associated with PPI reductions, when combined with rs2439272. CONCLUSIONS: We provide solid evidence for a role of NRG1 risk genotype variations in PPI reductions in a large and demographically and genetically highly homogeneous cohort of healthy young males. These results further validate NRG1 as a candidate gene for the schizophrenia and spectrum disorders and improve our understanding of its functional mechanisms within the human brain because they suggest an influence of the gene in the neural substrate mediating sensorimotor gating. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/21035784/The_influence_of_schizophrenia_related_neuregulin_1_polymorphisms_on_sensorimotor_gating_in_healthy_males_ DB - PRIME DP - Unbound Medicine ER -