Related Experiment Video
Updated: Sep 10, 2025

Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing ChIP-seq
Published on: April 19, 2013
Unveiling CTRB2, RSPO3, KLOTB, and ROR1 as obesity-pancreatic disease association proteins: a comprehensive Mendelian
Chunhua Zhou1, Xixian Ruan2, Tianyi Che1
1Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Background:
Obesity is recognized as a prominent contributing factor for pancreatic diseases; however, the mechanisms remain elusive. We aimed to identify the mediating role of circulating proteins in these associations.
Methods:
A two-step Mendelian randomization (MR) was conducted to investigate associations between nine obesity indicators, thousands of circulating proteins, with three pancreatic diseases (acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma). Colocalization analyses were performed to validate these associations. Protein mediating networks among obesity indicators and pancreatic diseases were investigated by mediation analysis.
Results:
Genetically predicted circulating levels of 4, 2, and 2 proteins were associated with acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma, respectively. In mediation analysis, decreased chymotrypsin B2 (CTRB2) levels mediated 1.03% (95% CI [confidence interval] 0.02%-2.03%) of the effects of body mass index on acute pancreatitis. Increased R-spondin 3 (RSPO3) levels mediated the effects of body mass index (2.95%, 95% CI 0.18%-5.73%), body fat percentage (4.53%, 95% CI 1.11%-7.96%), waist-hip ratio (8.48%, 95% CI 3.11%-13.86%), and visceral adipose tissue (3.93%, 95% CI 0.64%-7.22%) on acute pancreatitis. We also found increased klotho beta (KLOTB) levels mediated the effects of waist-hip ratio (7.01%, 95% CI 3.30%-10.71%) and visceral adipose tissue (8.98%, 95% CI 4.55%-13.41%) on chronic pancreatitis, and decreased receptor tyrosine kinase-like orphan receptor 1 (ROR1) levels mediated the effects of body mass index (10.39%, 95% CI 3.36%-17.42%) and visceral adipose tissue (6.29%, 95% CI 1.00%-11.58%) on pancreatic carcinoma.
Conclusions:
The MR suggests that circulating CTRB2, RSPO3, KLOTB, and ROR1 proteins may mediate associations between obesity and pancreatic diseases.
More Related Videos
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Pleiotropy
Single Nucleotide Polymorphisms-SNPs
Polygenic Traits

