Study Finds Genetic Link to Bipolar Disorder in Han Chinese

The objective of this study was to explore the genetic basis of bipolar disorder in the Han Chinese population.

An association between transmembrane protein 108 and bipolar disorder was found in Han Chinese participants in a genome-wide association study published in JAMA Psychiatry.

Most genome-wide association studies have been performed in Europeans. The researchers in the current study sought to identify genome-wide risk loci in Han Chinese.

The researchers recruited 6472 Han Chinese participants from mainland China. A sample of 958 individuals with bipolar disorder and 2050 controls were included. Genotyping in the discovery stage was performed with either the Illumina Infinium Global Screening Array (GSA) chip or the Illumina Genome-Wide Asian Screening Array (ASA) chip. The imputation reference set was obtained from phase 3 of the 1000 Genomes Project.

Analysis demonstrated that rs9863544 had genome-wide significance (P =2.49  10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756). In the GTEx data set, the mRNA of NPHP3-AS1 was barely detectable in most human organs, whereas TMEM108 was “widely expressed” in the human brain.

Based on studies in mice, the researchers concluded TMEM108-correlated physiological processes likely contribute to bipolar disorder pathogenesis. However, the Han Chinese genome-wide significant SNV rs9863544 and its surrounding variations did not show evidence of association with bipolar disorder in Europeans, which, the researchers said, suggests a Chinese-specific bipolar disorder risk locus.

Limitations include the fact that control participants were recruited based on self-reported health status rather than professional screening.

The authors conclude that their “study describes several novel risk loci for BD and a shared genetic basis for BD across Han Chinese and European populations.” They believe that further research is needed to more fully understand “the underlying pathological mechanisms.”


Li HJ, Zhang C, Hui L, et al; GeseDNA Research Team. Novel risk loci associated with genetic risk for bipolar disorder among Han Chinese individuals: A genome-wide association study and meta-analysis. JAMA Psychiatry. Published online December 2, 2020. doi:10.1001/jamapsychiatry.2020.3738