Associations of rare variants in the AKAP11 gene with bipolar disorder in Chinese population

Abstract

Abstract Purpose This pioneering study aimed to explore the associations between the A-kinase anchoring protein 11 (AKAP11) gene and bipolar disorder (BD) in a Chinese population. We sought to replicate findings from European populations regarding ultra-rare protein-truncating variants (PTVs) within exon 8 of AKAP11 and identify any novel rare mutations linked to Chinese BD patients. Methods We conducted a case-control association study, including a cohort of 284 Chinese BD patients, with the control group comprising 10,588 individuals from the China Metabolic Analytics Project (ChinaMAP) database. Polymerase chain reaction (PCR) amplification and Sanger sequencing were performed to analyze exon 8 of the AKAP11 gene. Statistical analysis involved chi-square tests to assess differences in allele frequency between BD patients and the control group. Results In our 284 Chinese BD patients, within exon 8 of the AKAP11 gene we did not find any ultra-rare PTVs previously identified in European BD patients. However, five additional rare variants were discovered, including three missense variants and two synonymous variants. Among these variants, one synonymous variant, g.42300171T > C (i.e., rs771987690), had not been reported in the ChinaMAP database. Statistical analysis did not reveal significant differences in allele frequencies between BD patients and controls (P = 0.240), but there was a noticeable trend suggesting a potential association between the rare variants with the AKAP11 gene and risk of BD. Additionally, three of the five rare variants were not documented in the Bipolar Exomes Browser (BipEx) database, the frequencies of the other two were mildly lower in cases than controls, contrary to the trend observed in the Chinese population. The observed difference may be due to population genetic-environmental interaction. Conclusions Our preliminary data indicates a potential trend between the AKAP11 gene and BD patients in China, despite did not reach nominal significance, calling for further analysis in a larger sample set.