Genetic Association between lipid and the risk of Headache

Abstract

Background Headache is one of the most prevalent neurological manifestation. Abnormal vascular function and activation of inflammatory responses increase the sensitivity of pain, which together affect pain processing pathways. Lipids perform a variety of critical functions, dysfunction of lipid metabolism and homeostasis can be involve in a variety of acute and chronic diseases. However, the exact association between lipids and headache still remains unknown due to various challenges. This study aimed to investigate the potential causal association between lipids and headache by using a two-sample Mendelian randomization (TSMR) analysis. Methods Utilizing a two-sample Mendelian randomization (MR) analysis, this study analyzed genome-wide association study (GWAS) data pertaining to 179 lipid traits to explore their causal links with four prevalent headache disorders: tension-type headache (TTH), migraine, cluster headache, and medication-overuse headache (MOH). A suite of MR analytical methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode were employed to ascertain the robustness of the causal conclusions. To further validate these findings, sensitivity analyses were conducted. Results The MR analysis demonstrated significant causal associations between several lipid species and headache disorders. Increased genetic predisposition to specific lipid levels, such as diacylglycerol and triacylglycerol, was linked with a higher risk of developing TTH and migraine. Contrasting effects were observed with phosphatidylcholine; certain species conferred protection against cluster headaches, while others were associated with increased risks of TTH and migraine. The associations remained consistent across different MR methods and were statistically significant after adjustments for multiple testing. Conclusion The MR analysis suggests a potential causal relationship between lipids and the risk of headache including TTH, migraine, cluster headache and MOH. However, further extensive research involving diversified populations is imperative to validate these findings.