Table of Contents

ABSTRACT

Bipolar disorder (BD), also known as manic depression, is a severe mood disorder that causes shifts in mood, energy and ability to function. While there is no cure currently, many people with bipolar disorder could be treated and with the right medication, could go into remission and be symptom free for years or decades. It is estimated that BD affects 2.4% of the population worldwide. Patients of BD suffer from recurrent episodes of mania and depression with each episode typically lasting for 1 to 2 weeks. As a result, patients’ lives are severely disrupted. Studies have shown that it is a complex mental disease which is highly heritable, polygenic yet multifactorial. So far vast numbers of candidate genes have been implicated for BD and several models have been proposed to explain the pathology of BD: ion channel pathology (ANK3, CACNA1C and GABRB2), disruption of signaling pathways (BDNF, DGKH, NTRK2 and NRG1), abnormal cell-cell adhesion (FAT1, CTNNA2, CDH7 and NCAN), and disruption in circadian rhythm (CLOCK, ARNNTL and TIMELESS). Concerning the epigenetic studies of BD, differential DNA methylation has been observed in both coding genes (HTR1A, MB-COMT CTNNA2 and MHR1) and non-protein coding gene (HCG9). In addition to specific gene candidates, some studies attempt to find the link between BD and epigenetic modification.

Keywords: GWAS, SNPs, Association study, DNA methylation, ion channel, signaling pathway, cell adhesion