Associations of Rare Variants in the AKAP11 Gene with Bipolar Disorder in Chinese Population
Bibliographic record
Abstract
Yankai Zhang, Chunhui Qu, Tingting Wang, Xiangwen Wang, Shunkang Feng, Ping Sun Department of Mood Disorders, Qingdao Mental Health Center, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Ping Sun, Department of Mood Disorders, Qingdao Mental Health Center, Qingdao, 266000, People’s Republic of China, Tel +86 13589394393, Email qdsunping99@sina.comPurpose: 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 on VassarStats to assess allele frequency differences between BD patients and the control group, along with power analysis using PASS (version 21.0.3).Results: In 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. Notably, rs2236364 showed concordant deleterious predictions across four computational tools, warranting prioritized investigation. Statistical analysis revealed no significant difference in allele frequencies between groups (P= 0.240), although a slightly higher proportion of rare variants was observed in cases versus controls. Additionally, three 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.Conclusion: In this pioneering Chinese population study of BD-AKAP11, we did not replicate the association of ultra-rare PTVs but identified five additional rare variants. Population-specific distribution patterns—exemplified by rs2236364 with computationally deleterious predictions—warrant validation in expanded cohorts to elucidate trans-ethnic risk mechanisms.Keywords: bipolar disorder, AKAP11, East Asian People, rare mutation, case-control studies
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".