Genetic Association of Lipids and Lipid-Lowering Drug Target Genes With Attention Deficit Hyperactivity Disorder.

IF 2.7 3区医学 Q2 PSYCHIATRY Journal of Attention Disorders Pub Date : 2024-09-01 Epub Date: 2024-01-03 DOI:10.1177/10870547231222219

Detong Guo, Wenchao Sheng, Yingzi Cai, Jianbo Shu, Chunquan Cai

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Abstract

Background: 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.

Methods: 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.

Results: 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 APOB-mediated low-density lipoprotein cholesterol was associated with lower ADHD risk (odds ratio [OR] = 0.90, 95% confidence interval [CI] [0.84, 0.97]; p = .007), whereas LPL-mediated triglycerides levels were associated with a higher risk of ADHD (OR = 1.13, 95% CI [1.06, 1.21]; p < .001).

Conclusion: Our results suggest that APOB gene and LPL gene may be candidate drug target genes for the treatment of ADHD.

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血脂和降脂药物靶基因与注意力缺陷多动障碍的遗传关系。

背景：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。人们一直在努力寻找与多动症相关并与之有因果关系的生物标志物，其中血脂是一个可能的致病因素，研究相当广泛。我们旨在利用孟德尔随机化（MR）研究评估血脂特征、降脂药物和注意缺陷多动障碍（ADHD）结果之间的因果关系：我们利用全基因组关联研究的汇总数据来探讨循环血脂相关性状与多动症之间的因果关系。然后，提取降脂药物靶基因表达的定量性状位点以及与血脂性状相关的遗传变异。采用基于汇总数据的MR和反方差加权MR（IVW-MR）研究这些药物靶基因的表达与ADHD之间的相关性：结果：经过严格筛选，939个工具变量最终被纳入单变量泯灭随机分析。然而，血脂谱与多动症风险之间没有相关性。通过 IVW-MR 方法进行的药物目标分析发现，APOB 介导的低密度脂蛋白胆固醇与较低的多动症风险相关（比值比 [OR] = 0.90，95% 置信区间 [CI] [0.84, 0.97]；P = .007），而 LPL 介导的甘油三酯水平与较高的多动症风险相关（比值比 [OR] = 1.13，95% 置信区间 [CI] [1.06, 1.21]；P 结论：我们的研究结果表明，APOB 基因和 LPL 基因可能是治疗多动症的候选药物靶基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Attention Disorders PSYCHIATRY-

CiteScore

7.60

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Journal of Attention Disorders (JAD) focuses on basic and applied science concerning attention and related functions in children, adolescents, and adults. JAD publishes articles on diagnosis, comorbidity, neuropsychological functioning, psychopharmacology, and psychosocial issues. The journal also addresses practice, policy, and theory, as well as review articles, commentaries, in-depth analyses, empirical research articles, and case presentations or program evaluations.