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. 2024 Feb 12;18(1):19.
doi: 10.1186/s40246-024-00583-y.

Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses

Jiarui Mi #  1 , Qingwei Jiang #  2 , Zhengwei Qi #  1 , Zhengye Liu #  3 , Xiaoyin Bai  2 , Xia Zheng  1 , Jiaguo Wu  1 , Yanfei Fang  1 , Aiming Yang  2 , Haotian Chen  4
Affiliations

Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses

Jiarui Mi et al. Hum Genomics. .

Abstract

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

Keywords: Campesterol; Cholecystitis; Cholelithiasis; Colocalization analysis; Genome-wide association study; Mendelian randomization; Risk factor.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Heatmap showing the causal estimates of metabolites (with valid SNPs as instrumental variables ≤ 3) on the risk of cholelithiasis and cholecystitis using IVW fixed effect model. The p-value is adjusted using Bonferroni method. IVW, inverse-variance weighted; R9, FinnGen Release 9; UKBB, UK Biobank
Fig. 2
Fig. 2
Colocalization analyses indicating the highlighted SNPs in campesterol (A) and cholelithiasis (B). The SNPs with significant p-value are located at the ABCG8 and ABCG5 loci. Notes: ABCG5, ATP Binding Cassette Subfamily G Member 5; ABCG8, ATP Binding Cassette Subfamily G Member 8
See this image and copyright information in PMC

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