PhD Scientific Days 2017

Poster Presentation: Neurosciences

P49: SORCS3 gene replicated in the gene-based genomic background of neuroticism

Előadó neve

Dr. Eszlári, Nóra

Előadó munkahelye

Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University

Előadó telefonszáma

+36304902112

Előadó e-mail címe

eszlari.nora@gmail.com

Az előadás címe

SORCS3 gene replicated in the gene-based genomic background of neuroticism

Szerző(k) neve és munkahelye

Nóra Eszlári1,2,3, András Millinghoffer2,3,4, Péter Petschner1,2,3, Xénia Gonda2,3,5, Dániel Baksa2,6, Péter Antal2,3,4, György Bagdy1,2,3, Gabriella Juhász1,2,3,6,7
1 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary;
2 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;
3 NAP-A-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary;
4 Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary;
5 Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Centre, Semmelweis University, Budapest, Hungary;
6 MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;
7 Neuroscience and Psychiatry Unit, Institute of Brain Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom

Szekció

Poster Presentation: Neurosciences

Data of the presenter

Doctoral School: Doctoral School of Mental Health Sciences
Program: Psychiatry
Supervisor: Gabriella Juhász
Email: eszlari.nora@gmail.com

Supported by the ÚNKP-16-3 New National Excellence Program of The Ministry of Human Capacities.

Text of the abstract

Introduction. Neuroticism has been denoted as a risk factor for major depression, and to have a considerable genetic correlation with it. Genome-wide association studies (GWAS) have been carried out to reveal new candidates in the genetic background of neuroticism, both at single nucleotide polymorphism (SNP) level and gene level. However, in these studies, gene-level associations were carried out with only one method.
Aims. In the present study we compared different gene-level analysis methods, incorporating different biological assumptions, to identify replicable results.
Methods. In our GWAS, we investigated the association of neuroticism with 86,232 SNPs genotyped directly and located across the whole genome, among a European white sample (N=1770). Results were then aggregated by the GATES method to gain gene-level results. Both SNP-level and gene-level results were corrected for multiple testing by the false discovery rate (FDR) method at an error rate of 0.05. In addition, four gene-level tests were applied according to FORGE and SETSCREEN methods, to replicate the primary findings.
Results. None of the SNP-level results survived FDR correction. 63,326 SNPs (64.46%) reside within genes, and none of the 18,264 gene-level statistics survived the FDR correction. Yet, among the more than fifty genes having been associated with neuroticism by previous GWAS studies, SORCS3 (sortilin related VPS10 domain containing receptor 3) and TACC2 (transforming acidic coiled-coil containing protein 2) genes showed nominally significant (p≤0.05) association with neuroticism in our study. The effect of TACC2 was not significant according to additional gene-level tests, while SORCS3 showed nominally significant effect on neuroticism with all four replication methods.
Conclusion. Our GWAS is the first one to demonstrate the association of the SORCS3 gene with neuroticism at gene level with multiple methods, extending previous SNP-level findings. SORCS3 is highly expressed in the brain and is a candidate for other neuropsychiatric disorders.

Azonosító

P49

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1049

Authors (legacy)

Nóra Eszlári1,2,3, András Millinghoffer2,3,4, Péter Petschner1,2,3, Xénia Gonda2,3,5, Dániel Baksa2,6, Péter Antal2,3,4, György Bagdy1,2,3, Gabriella Juhász1,2,3,6,7
1 Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary;
2 MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;
3 NAP-A-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary;
4 Department of Measurement and Information Systems, Budapest University of Technology and Economics, Budapest, Hungary;
5 Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Centre, Semmelweis University, Budapest, Hungary;
6 MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;
7 Neuroscience and Psychiatry Unit, Institute of Brain Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom