DOI: 10.1097/js9.0000000000005025 ISSN: 1743-9159

Investigating the shared genetic architecture between digestive diseases and cardiovascular diseases

Jiaqi Li, Haoyang Zhang, Jieyi Chen, Huiyao Chen, Zhongmeng Xiong, Ting Peng, Xinran Dong, Lin Yang, Wenhao Zhou, Zewen Li
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Background:

The link between digestive diseases (DGDs) and cardiovascular diseases (CVDs) is growing, but their genetic ties are not well understood.

Methods:

We analyzed large-scale genome-wide association study (GWAS) data to explore shared genetic architectures between 20 DGDs and 29 CVDs. Genetic correlations and overlaps were assessed using linkage disequilibrium score regression (LDSC) and generalized pleiotropic analysis (GPA). Polygenic risk scores (PRS) and two-sample Mendelian randomization (MR) analyses were used to evaluate causal relationships. Multi-trait analysis of GWAS (MTAG) identified single nucleotide polymorphisms (SNPs) linked to these relationships, while summary data-based Mendelian randomization (SMR) and multi-marker analysis of genomic annotation analyses pinpointed specific tissues and cell types involved.

Results:

LDSC, GPA, and PRS analyses showed widespread genetic associations between DGDs and CVDs. MR analysis revealed causal effects of ulcerative colitis on deep vein thrombosis of lower extremities ( β  = 0.04, P = 0.04) and atrioventricular block (AVB; β  = 0.06, P = 0.005), acute appendicitis on heart failure ( β  = 0.13, P = 0.03), ischemic stroke ( β  = 0.16, P = 0.003), and stroke ( β  = 0.14, P = 0.02). Shared genetic architectures and novel SNPs linked to genes such as ABCG5 and ABCG8 for cholelithiasis-coronary artery disease, LTBR for acute appendicitis-heart failure, acute appendicitis-stroke, and acute appendicitis-ischemic stroke, GNA12 and SMAD3 for ulcerative colitis–AVB, and GSDMA for ulcerative colitis-deep vein thrombosis of lower extremities were also identified.

Conclusion:

This study suggests that genetic susceptibility to certain DGDs may increase CVD risk, providing insights for clinical strategies to prevent CVDs in patients with DGDs.

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