en Genetics & Disease Genetics & Disease Short Communication Short Communication Bipolar disorder (BD) is a major health care concern worldwide. There are some reports showing an association between genes and their variants involved in circadian rhythm; clock and clock related genes function and development of BD in patients.&nbsp; Therefore, the aim of this study was to investigate the possible association of rs534654 variant on<em> TMEM165</em> (transmembrane protein 165) gene with the risk of BD. Genotyping of the rs534654 was carried out using the tetra primers- amplification refractory mutation system-PCR (4P-ARMS-PCR) method in 203 patients with BD type 1 and their healthy and normal counterpart. The frequency of the G and A alleles of rs534654 polymorphism was 53% and 47%, respectively in patients. Genotype frequency in patients in comparison with control subjects was 5.4% vs 2.5% for the AA homozygous; 11.3% vs 80.8% for the GG homozygous; and 83.3% vs 16.7% for the heterozygous AG. Statistical analysis showed a significant difference in frequencies between the control and patient groups (P = 0.001). Based on this finding, it is possible to conclude that the impairment in the rs534654 single nucleotide polymorphism in <em>TMEM165</em> gene is associated with the risk of BD development. Bipolar disorder, genetics polymorphism, TMEM165 155 162 http://ijmcmed.org/browse.php?a_code=A-10-3894-1&slc_lang=en&sid=1 Asmaolhosna Amini asmaolhosnaamini@gmail.com 100319475328460021213 100319475328460021213 No Sara Medical Genetic Laboratory, Tehran, Iran. Sara Sadat Aghabozorg Afjeh s.afjeh@yahoo.com 100319475328460021214 100319475328460021214 No Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Behzad Boshehri behzadboshehri@yahoo.com 100319475328460021215 100319475328460021215 No Department of Forensic Medicine and Toxicology, Urmia University of Medical Sciences, Urmia, Iran. Safar Hamednia dr.hamednia@yahoo.com 100319475328460021216 100319475328460021216 No Department of Psychiatry, Urmia University of Medical Sciences, Urmia, Iran. Parisa Mashayekhi parisamashayekhi7@gmail.com 100319475328460021217 100319475328460021217 No Tajrish Research Center Pasteur Institute of Iran, Tehran, Iran. Mir Davood Omrani davood_omrani@yahoo.co.uk 100319475328460021218 100319475328460021218 Yes Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.