Novel Risk Genes Identified for Bipolar Disorder

Bipolar disorder (BD) is a common psychiatric disorder characterized by mood swings between positive manic/hypomanic and negative/depressive states, with a lifetime prevalence of more than 1%.

Although epidemiological studies indicate that genetic components contribute to BD development, several genome-wide association studies (GWAS) identified limited number of susceptibility (risk) genes for BD, most of which are yet unidentified.

A collaboration of scientists under the auspices of those at Fujita Health University performed GWAS on 1,612 BD subjects, with 1,545 BD cases remaining after genotype quality control (QC) (Phase I); and the Phase II GWAS initially included 1,604 BD subjects, with 1,419 BD cases remaining after QC. For the Phase I study, the controls comprised 7,408 subjects who were genotyped in a previous GWAS as case subjects for five non-psychiatric disorders (cerebral aneurysm, esophageal cancer, endometrial cancer, chronic obstructive pulmonary disease and glaucoma) or as healthy volunteers. The controls for the Phase II study included 54,479 subjects who had also been genotyped as case subjects for 14 non-psychiatric disorders.

Genotyping was performed using the Illumina HumanOmniExpress v1 chip. The investigators identified a novel risk gene fatty acid desaturase genes (FADS1 and FADS2) for bipolar disorder via GWAS performed using samples collected in Japan of 2,964 cases and 61,887 comparison subjects. The function of this gene is well established: metabolism of lipids, including blood lipids (e.g., cholesterol and triglyceride) and omega3/6 polyunsaturated fatty acids (PUFA). The team then then conducted a meta-analysis between their samples and results from the publicly available BD GWAS database. They identified an additional novel gene for BD, nuclear family I/X (NFIX), and supported three previously implicated genes. The BD ‘risk’ effect is shared between Japanese and European populations. The study was published on January 24, 2017, in the journal Molecular Psychiatry.