Related Experiment Video
Updated: Jul 13, 2026
08:46
Forward Genetic Screen Using Transgenic Calcium Reporter Aequorin to Identify Novel Targets in Calcium Signaling
Published on: August 1, 2020
Calcium signaling pathway implicates a shared genetic basis between psychiatric and cardiovascular diseases
Yunqing Zhu1, Guorui Zhao1, Yuyanan Zhang1
1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China.
Translational Psychiatry
|July 11, 2026
Summary
This study reveals shared genetic links between psychiatric disorders and cardiovascular diseases (CVDs) in East Asians. Findings suggest caution with calcium channel blockers in patients with both conditions.
Area of Science:
- Genetics
- Psychiatry
- Cardiology
- Pharmacogenomics
Background:
- Psychiatric and cardiovascular diseases (CVDs) frequently co-occur, linked by the brain-heart axis.
- The shared genetic basis for these comorbidities, particularly in East Asian populations, is largely unknown.
- Understanding this genetic overlap is crucial for developing integrated treatment strategies.
Purpose of the Study:
- To investigate the shared genetic etiology between major psychiatric disorders and cardiovascular traits in East Asians.
- To identify pleiotropic loci and genes contributing to the comorbidity of psychiatric and cardiovascular diseases.
- To explore the clinical implications of these genetic findings, particularly regarding drug therapies.
Main Methods:
- Conducted a genome-wide pairwise trait pleiotropy study using GWAS data for schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), and ten cardiovascular traits in East Asians.
- Performed cross-ancestry replication of identified pleiotropic loci.
- Analyzed tissue-specific gene expression, validated the calcium signaling pathway, and conducted drug target analysis using gene expression profiles.
Main Results:
- Identified significant genetic overlaps between seven pairs of psychiatric and cardiovascular diseases, including SCZ and coronary artery disease.
- Six pleiotropic loci showed tissue-specific expression in brain and cardiovascular systems; nine loci were validated in cross-ancestry replication.
- Novel pleiotropic genes, such as TPCN1 and CACNA2D2, implicated in calcium channel activity. A polygenic risk score for SCZ based on the calcium pathway associated with prolonged QTc interval.
- Drug target analysis indicated calcium-channel blockers and peripheral vasodilators may increase SCZ risk, while diuretics may reduce risks for SCZ, BIP, and MDD.
Conclusions:
- Revealed extensive shared genetic architecture between psychiatric disorders and CVDs in East Asian populations.
- Highlighted the role of calcium signaling pathways in the comorbidity of these conditions.
- Warrants caution in prescribing calcium channel blockers for individuals with co-occurring psychiatric and cardiovascular diseases, suggesting potential genotype-guided therapeutic strategies.
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