Tianjin Children's Hospital (Tianjin University Children's Hospital), China.
Tianjin Medical University, China.
J Atten Disord. 2024 Sep;28(11):1425-1436. doi: 10.1177/10870547231222219. Epub 2024 Jan 3.
Lipid metabolism plays an essential role in nervous system development. Cholesterol deficiency leads to a variety of neurodevelopmental disorders, such as autism spectrum disorder and fragile X syndrome. There have been a lot of efforts to search for biological markers associated with and causal to ADHD, among which lipid is one possible etiological factor that is quite widely studied. We aimed to evaluate the causal relationship between lipids traits, lipid-lowering drugs, and attention deficit hyperactivity disorder (ADHD) outcomes using Mendelian randomization (MR) studies.
We used summary data from genome-wide association studies to explore the causal relationships between circulating lipid-related traits and ADHD. Then, quantitative trait loci for the expression of lipid-lowering drug target genes and genetic variants associated with lipid traits were extracted. Summary-data-based MR and inverse-variance-weighted MR (IVW-MR) were used to investigate the correlation between the expression of these drug-target genes and ADHD.
After rigorous screening, 939 instrumental variables were finally included for univariable mendelian randomization analysis. However, there is no correlation between lipid profile and ADHD risk. Drug target analysis by IVW-MR method observed that -mediated low-density lipoprotein cholesterol was associated with lower ADHD risk (odds ratio [] = 0.90, 95% confidence interval [CI] [0.84, 0.97]; = .007), whereas -mediated triglycerides levels were associated with a higher risk of ADHD ( = 1.13, 95% CI [1.06, 1.21]; < .001).
Our results suggest that gene and gene may be candidate drug target genes for the treatment of ADHD.
脂质代谢在神经系统发育中起着至关重要的作用。胆固醇缺乏会导致多种神经发育障碍，如自闭症谱系障碍和脆性 X 综合征。人们已经做了很多努力来寻找与 ADHD 相关和因果关系的生物标志物，其中脂质是一个被广泛研究的可能的病因因素。我们旨在使用孟德尔随机化（MR）研究评估脂质特征、降脂药物与注意力缺陷多动障碍（ADHD）结果之间的因果关系。
我们使用全基因组关联研究的汇总数据来探索循环脂质相关特征与 ADHD 之间的因果关系。然后，提取降脂药物靶基因表达的数量性状基因座和与脂质特征相关的遗传变异。使用基于汇总数据的 MR 和逆方差加权 MR（IVW-MR）来研究这些药物靶基因表达与 ADHD 之间的相关性。
经过严格筛选，最终纳入了 939 个工具变量进行单变量孟德尔随机化分析。然而，脂质谱与 ADHD 风险之间没有相关性。通过 IVW-MR 方法进行的药物靶标分析观察到，-介导的低密度脂蛋白胆固醇与较低的 ADHD 风险相关（比值比[]=0.90，95%置信区间[CI] [0.84, 0.97]；=0.007），而-介导的甘油三酯水平与 ADHD 风险升高相关（=1.13，95%CI [1.06, 1.21]；<0.001）。
我们的结果表明，基因和基因可能是治疗 ADHD 的候选药物靶基因。
