Mendelian randomization study of lipid metabolism characteristics and migraine risk

IF 3.5 2区医学 Q1 ANESTHESIOLOGY European Journal of Pain Pub Date : 2024-01-06 DOI:10.1002/ejp.2235

Peiwei Hong, Lin Han, Yang Wan

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Abstract

Background

The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk.

Methods

Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk.

Results

Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000).

Conclusions

There is a relationship between lipid metabolism characteristics and migraine risk.

Significance

Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

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脂质代谢特征与偏头痛风险的孟德尔随机研究

背景：血清脂质与偏头痛之间的关系存在争议。然而，随机对照试验表明，他汀类药物可有效预防偏头痛。本研究旨在探讨血脂代谢与偏头痛风险之间的关系：从全基因组关联研究（GWAS）摘要数据中提取了与血清脂质特征和针对 APOB、CETP、HMGCR、NPC1L1 和 PCSK9 的降脂药物效果有关的单核苷酸多态性（SNPs）。全基因组关联研究（GWAS）摘要数据分别来自全球血脂基因联盟（GLGC）、英国生物库（UK Biobank）和芬兰基因研究（FinnGen）。研究人员进行了孟德尔随机化（MR）分析，以评估血清脂质特征和降脂药物与偏头痛风险之间的关联：结果发现：在血清脂质方面，与高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）、总胆固醇（TC）或甘油三酯（TG）水平相关的SNPs与偏头痛、先兆性偏头痛（MA）或无先兆性偏头痛（MO）无关。此外，与低密度脂蛋白胆固醇（LDL-C）水平较高有关的 HMGCR 基因型与偏头痛（OR = 1.46，p = 0.035）和 MA（OR = 2.03，p = 0.008）风险增加有关；然而，与低密度脂蛋白胆固醇（LDL-C）水平较高有关的 PCSK9 基因型与偏头痛风险降低有关（OR = 0.75，p = 0.001）和 MA（OR = 0.69，p = 0.004）；而与较高 LDL-C 水平相关的 APOB 基因型与 MO 风险降低相关（OR = 0.62，p = 0.000）：结论：脂质代谢特征与偏头痛风险之间存在关系：根据全基因组关联汇总数据，与高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）、总胆固醇（TC）或甘油三酯（TG）水平相关的单核苷酸多态性（SNPs）与偏头痛、有先兆偏头痛（MA）或无先兆偏头痛（MO）的风险无关。然而，与低密度脂蛋白胆固醇（LDL-C）水平较高相关的 HMGCR 基因型却显示偏头痛和先兆性偏头痛的风险增加。而与低密度脂蛋白胆固醇（LDL-C）水平较高相关的 APOB 或 PCSK9 基因型则分别显示出对 MO 或偏头痛和 MA 的风险降低。这些结果表明，脂质代谢特征与偏头痛发病风险之间可能存在某种关系。

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来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.