A genetic correlation analysis between addiction-related traits and chronic bowel disorders

Abstract

Abstract Aims Addiction is currently seen as a neuropsychiatric disorder with genetic component involved. Multiple chronic bowel disorders could exert influence on mental status including addition. This study aims to investigate the genetic correlation of addiction-related traits and chronic bowel disorders. Methods We extracted addiction-related traits information from UK Biobank database. We then calculated the polygenic risk score (PRS) of chronic bowel disorders (ulcerative colitis (UC), Crohn’s disease (CD), UC + CD and irritable bowel syndrome (IBS) respectively) for each individual. A regression analysis was conducted to measure the correlation of addiction-related traits and chronic bowel disorder PRS. We further performed a linkage disequilibrium score regression to evaluated the genetic correlation of chronic bowel disorders (UC, CD) and addiction traits (alcohol dependence) in another public GWAS datasets. Lastly, a genome-wide genetic interaction study (GWGIS) was conducted to measure the interactive effects of chronic bowel disorders (UC, UC + CD) and genetic variants in addiction-related traits. Results Regression analysis identified positive correlation at CD PRS and “ever addicted to any substance or behavior” (P = 4.80×10− 2, beta = 0.141), CD PRS and “ever addicted to alcohol” (P = 1.90×10− 2, beta = 1.533), and UC + CD PRS and “ever addicted to alcohol” (P = 2.70×10− 2, beta = 0.882). LDSC analysis detected a significant genetic correlation at CD and alcohol dependence (P = 8.60×10− 3). GWGIS results revealed that a group of significant genetic variations, such as rs12063422 (P = 4.15×10− 6), showed interactive effect with CD PRS in alcohol addiction. Conclusions Our results revealed a genetic correlation between CD and alcohol addiction, which might be partly attributed to accumulated effect of a number of associated SNPs.