No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese patients Masashi Ikeda a,b, * , Nakao Iwata a , Tatsuyo Suzuki a , Tsuyoshi Kitajima a , Yoshio Yamanouchi a , Yoko Kinoshita a , Toshiya Inada b , Norio Ozaki b a Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan b Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya 466-8850, Japan Received 27 April 2005; received in revised form 2 May 2005; accepted 4 May 2005 Available online 20 June 2005 Abstract Recent study of linkage disequilibrium mapping showed one of the trace amine receptor (TRAR) genes, TRAR4, was associated with schizophrenia. We conducted a replication study of TRAR4 with schizophrenia in Japanese patients. We used two large independent sets of samples in a first-set analysis (cases = 405, controls = 401) and second-set analysis (cases = 503, controls = 440). In the first-set analysis, one Marker (Marker5) showed a significant association, but this significance was not seen in the second-set analysis. Our results indicate that TRAR4 may not play a major role in Japanese schizophrenia patients, and that it is important to examine the possibility of false positives in genetic association analysis. D 2005 Elsevier B.V. All rights reserved. Keywords: Schizophrenia; Trace amine receptor; Linkage disequilibrium; Haplotype-tagging SNP 1. Introduction Trace amines (TAs) are endogenous amine com- pounds that are chemically similar to classic biogenic amines. TAs were thought to be dfalse transmittersT which displace classic biogenic amines from their storage and act on transporters in a fashion similar to the amphetamines, but the identification of brain receptors specific to TAs indicates that they also have effects of their own effects, and TA receptors bind several psychostimulants such as amphetamine and d- lysergic acid diethylamide (LSD) (Parker and Cubeddu, 1986). A recent study of linkage disequilibrium (LD) mapping showed significant association between SNPs in one trace amine receptor (TRAR) gene TRAR4 and schizophrenia (SCZ) (Duan et al., 2004). By genotyping 192 pedigrees with SCZ of European or African American ancestry, from samples that previously showed linkage evidence to 6q13– 0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2005.05.002 * Corresponding author. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; fax: +81 562 93 1831. E-mail address: ikeda-ma@fujita-hu.ac.jp (M. Ikeda). Schizophrenia Research 78 (2005) 127 – 130 www.elsevier.com/locate/schres