ABSTRACT Suicidal thoughts during antidepressant treatment have been the focus of several candidate gene association studies. The aim of the present genome-wide association study was to

identify additional genetic variants involved in increasing suicidal ideation during escitalopram and nortriptyline treatment. A total of 706 adult participants of European ancestry, treated

for major depression with escitalopram or nortriptyline over 12 weeks in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study were genotyped with Illumina Human 610-Quad

Beadchips (Illumina, San Diego, CA, USA). A total of 244 subjects experienced an increase in suicidal ideation during follow-up. The genetic marker most significantly associated with

subjects treated with escitalopram. Suggestive drug by gene interactions for two SNPs near structural variants on chromosome 4q12, one SNP in the apolipoprotein O (_APOO_) gene on chromosome

Xp22.11 and one on chromosome 11q24.3 were found. The most significant association within a set of 33 candidate genes was in the neurotrophic tyrosine kinase receptor type 2 (_NTRK2_) gene.

Finally, we also found trend for an association within genes previously associated with psychiatric phenotypes indirectly linked to suicidal behavior, that is, _GRIP1_, _NXPH1_ and _ANK3_.

The results suggest novel pathways involved in increasing suicidal ideation during antidepressant treatment and should help to target treatment to reduce the risk of this dramatic adverse

event. Limited power precludes definitive conclusions and replication in larger sample is warranted. Access through your institution Buy or subscribe This is a preview of subscription

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ACKNOWLEDGEMENTS We acknowledge the contribution of Maja Bajs, Mara Barreto, Cristian Bonvicini, Desmond Campbell, Elzbieta Cegielska, Monika Dmitrzak-Weglarz, Amanda Elkin, Caterina

Giovannini, Joanna M Gray, Cerisse Gunasinghe, Bhanu Gupta, Sudhir Kumar, Susanne Höfels, Petra Kalember, Paweł Kapelski, Zrnka Kovacic, Dejan Kozel, Anna Leszczynska-Rodziewicz, Sylvie

Linotte, Andrej Marusic, Julien Mendlewicz, Metka Paragi, Laura Pedrini, Jorge Perez, Ute Pfeiffer, Aleksandra Rajewska-Rager, Luciana Rillosi, Christine Schmäl, Anna Schuhmacher, Maria

Skibiñska, Rebecca Smith, Farzana Hoda, Jana Strohmaier, Jerneja Sveticic, Aleksandra Szczepankiewicz, Alenka Tancic, Sandra Weber, Thomas Schulze, Piotr Czerski and Richard J Williamson.

The GENDEP study was funded by a European Commission Framework 6 grant, EC Contract Ref: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the

GENDEP study. GlaxoSmithKline, the Medical Research Council and the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and South London

and Maudsley NHS Foundation Trust (funded by the National Institute for Health Research, Department of Health, UK) contributed by funding add-on projects in the London center. The genotyping

was funded by joint grant from the Medical Research Council, UK and GlaxoSmithKline (G0701420). The fund providers had no role in the design and conduct of the study, in data collection,

analysis, interpretation or writing the report. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's

College London, London, UK N Perroud, R Uher, M Y M Ng, A Farmer, G Breen, K J Aitchison, C M Lewis, I W Craig & P McGuffin * Department of Psychiatry, University of Geneva Medical

School, Geneva, Switzerland N Perroud & M Guipponi * University Hospitals of Geneva, Geneva, Switzerland N Perroud & M Guipponi * Department of Genetic Medicine and Development,

University of Geneva Medical School, Geneva, Switzerland M Guipponi * Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland J

Hauser * Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia N Henigsberg * Department of Psychiatry, University of Bonn, Bonn, Germany W Maier *

Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark O Mors * Biological Psychiatry Unit and Dual Diagnosis ward IRCCS, Centro San Giovanni di Dio, FBF, Brescia,

Italy M Gennarelli * Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany M Rietschel * Laboratoire de Psychologie Médicale, Université Libre

de Bruxelles and Psy Pluriel—Centre Européen de Psychologie Médicale, Brussels, Belgium D Souery * Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia M Z Dernovsek

* Regionspsykiatrien Silkeborg, Aarhus University Hospital, Aarhus, Denmark A S Stamp * Centre National de Génotypage, Evry Cedex, France M Lathrop Authors * N Perroud View author

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for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to N Perroud. ETHICS DECLARATIONS COMPETING INTERESTS Perroud, Uher, Ng, Hauser, Guipponi, Maier, Mors,

Gennarelli, Rietschel, Dernovsek, Stamp, Lathrop, Breen, Craig and Lewis declare no competing interests. Henigsberg and Souery participated in clinical trials sponsored by pharmaceutical

companies including GlaxoSmithKline and Lundbeck. Henigsberg has received honoraria for participating in expert panels for pharmaceutical companies. Aitchison, Farmer and McGuffin have

received consultancy fees and honoraria for participating in expert panels for pharmaceutical companies including Lundbeck and GlaxoSmithKline. ADDITIONAL INFORMATION Supplementary

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R., Ng, M. _et al._ Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. _Pharmacogenomics J_ 12, 68–77 (2012).

https://doi.org/10.1038/tpj.2010.70 Download citation * Received: 28 February 2010 * Revised: 21 June 2010 * Accepted: 05 August 2010 * Published: 28 September 2010 * Issue Date: February

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not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * suicidal ideation * antidepressants * genome-wide

association * suicidality * escitalopram * nortriptyline