Birthweight influences liver structure, function and disease risk: Evidence of a causal association

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2024-11, Vol.26 (11), p.4976-4988
• Main Authors: Peng, Lei, Shen, Jiajia, Li, Lurong, Liu, Jiahao, Jiang, Xingzhou, Zhang, Guoxin, Li, Yuanyuan
• Format: Article
• Language: English
• Subjects: Birth weight; birthweight; causal effect; Fasting; Fatty liver; Fetuses; Insulin; Laboratory testing; Liver diseases; liver fat; Magnetic resonance imaging; Mendelian randomisation; non‐alcoholic fatty liver disease; Single-nucleotide polymorphism; Structure-function relationships; Triglycerides
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.15910

Aim Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. Materials and Methods We extracted single nucleotide polymorphisms (SNPs) from genome‐wide association studies (GWAS) about direct foetal‐affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two‐step MR analysis was used to further assess and quantify the mediating effects of the mediators. Results When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non‐alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29–2.02, p