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• W4319074894 abstract "Abstract Background: The shared genetic etiology among nonalcoholic fatty liver disease (NAFLD), overweight/obesity and type 2 diabetes (T2D), three closely related diseases, has not yet been thoroughly investigated. We aimed to explore the shared genetic etiology and causal relationships between the 3 diseases. Methods: Using public large-scale genome-wide association study (GWAS) data, the shared genetics between NAFLD (case=8,434, control=770,180) and 5 obesity traits (n= 224,459~700,000)/5 glycemic traits (n=281,416~659,316) were conducted with linkage disequilibrium score regression and cross-phenotype association (CPASSOC). The causal associations were explored with Mendelian Randomization (MR). Results: We revealed 20 shared loci between NAFLD and obesity traits and 10 loci between NAFLD and glycemic traits (P<5×10 -8 ). Among them, 10 loci were not reported previously in any association with NAFLD/obesity/glycemic traits. Ten out of 11 reported variants [after removing the high LD ( r 2 ≥0.8)] were missense variants. Most shared loci with known function were involved in the metabolism of lipids. Positive causal effects of obesity traits (particularly abdominal obesity) on NAFLD were detected, while NAFLD negatively impacted general obesity (BMI) and positively impacted abdominal obesity. Intriguingly, only fast insulin had a positive causal association with NAFLD and vice versa. Conclusions: Our study suggests that NAFLD, obesity and glycemic traits have shared genetic etiologies, particularly in the metabolism of lipids. The present work advances our understanding of the genetic basis of these 3 closely related diseases and sheds light on a new method for drug design." @default.
• W4319074894 created "2023-02-04" @default.
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• W4319074894 date "2023-02-03" @default.
• W4319074894 modified "2023-10-17" @default.
• W4319074894 title "Shared genetic etiology and causal relationships among NAFLD, obesity and glycemic traits: A large-scale genome-wide cross-trait analysis." @default.
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• W4319074894 doi "https://doi.org/10.21203/rs.3.rs-2517599/v1" @default.
• W4319074894 hasPublicationYear "2023" @default.
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