Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuropsychobiology 2012;66:134–140 DOI: 10.1159/000339559 Analysis of Four Genes Involved in the Neurodevelopment Shows Association of rs4307059 Polymorphism in the Cadherin 9/10 Region with Completed Suicide Izabela Chojnicka a Katarzyna Strawa a Sylwia Fudalej b Marcin Fudalej c Aleksandra Pawlak c Grażyna Kostrzewa a Marcin Wojnar b, d Paweł Krajewski c Rafał Płoski a Departments of a Medical Genetics, b Psychiatry and c Forensic Medicine, Medical University of Warsaw, Warsaw, Poland; d Department of Psychiatry, University of Michigan, Ann Arbor, Mich., USA genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049). Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort. Copyright © 2012 S. Karger AG, Basel Introduction Suicide is a significant cause of mortality with the an- nual rate from 1.1 to 54 deaths per 100,000 among Eu- ropean countries (http://www.who.int/mental_health/ prevention/suicide_rates/en/index.html#). The etiology of suicidal behavior is clearly multifacto- rial, but part of predisposition is determined by genetic factors [1–4]. Although a number of reports indicated that suicide risk is increased by variants of genes func- tioning in brain serotonergic systems, including trypto- phan hydroxylase 1 and 2 (TPH1 and TPH2) and sero- tonin transporter (5-HTT) [5–7], it is likely that other pre- disposing loci exist. Key Words rs4307059  rs930752  rs6265  rs10868235  Cadherin  BDNF  NTRK2  Neurexin  Genetic studies  Single nucleotide polymorphism Abstract Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9) , rs930752 (NRXN1) , rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide. Methodology: We used a case-control two-stage approach based on a discovery co- hort (557 cases and 550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Foren- sic Medicine, Medical University of Warsaw, Poland. Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymor- phism (OR 1.64, p = 0.012). The trend for an overrepresenta- tion of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonfer- roni correction (p cor. = 0.024). In an exploratory search for Received: October 6, 2011 Accepted after revision: May 21, 2012 Published online: July 27, 2012 Rafał Płoski, MD, PhD Department of Medical Genetics, Medical University of Warsaw ul. Pawińskiego 3c PL–02-106 Warsaw (Poland) Tel. +48 22 572 06 06, E-Mail rploski  @  wp.pl © 2012 S. Karger AG, Basel 0302–282X/12/0662–0134$38.00/0 Accessible online at: www.karger.com/nps