Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study
BackgroundPrevious research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.MethodsWe used genetic ins...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1331537/full |
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| author | Shicun Huang Yuan Liu Yi Zhang Yiqing Wang Ya Gao Runnan Li Lidong Yu Xiaowei Hu Qi Fang |
| author_facet | Shicun Huang Yuan Liu Yi Zhang Yiqing Wang Ya Gao Runnan Li Lidong Yu Xiaowei Hu Qi Fang |
| author_sort | Shicun Huang |
| collection | DOAJ |
| description | BackgroundPrevious research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.MethodsWe used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy.ResultsThe analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available.ConclusionThe drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition. |
| first_indexed | 2024-04-25T01:41:54Z |
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| language | English |
| last_indexed | 2024-04-25T01:41:54Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-37defd1c4c6440478ce69108f93829012024-03-08T04:42:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952024-03-011510.3389/fneur.2024.13315371331537Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization studyShicun Huang0Yuan Liu1Yi Zhang2Yiqing Wang3Ya Gao4Runnan Li5Lidong Yu6Xiaowei Hu7Qi Fang8Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Neurology, Suzhou Ninth People’s Hospital, Suzhou, ChinaDepartment of Neurology, The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, ChinaDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Neurology, Suzhou Guangci Cancer Hospital, Suzhou, ChinaDepartment of Neurology, The Dushu Lake Hospital of Soochow University, Suzhou, ChinaDepartment of Neurology, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Yangzhou, ChinaDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Neurology, First Affiliated Hospital of Soochow University, Suzhou, ChinaBackgroundPrevious research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.MethodsWe used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy.ResultsThe analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available.ConclusionThe drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.https://www.frontiersin.org/articles/10.3389/fneur.2024.1331537/fulllipid-lowering medicationsepilepsydrug target Mendelian randomizationcausalgeneticlipid metabolism |
| spellingShingle | Shicun Huang Yuan Liu Yi Zhang Yiqing Wang Ya Gao Runnan Li Lidong Yu Xiaowei Hu Qi Fang Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study Frontiers in Neurology lipid-lowering medications epilepsy drug target Mendelian randomization causal genetic lipid metabolism |
| title | Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study |
| title_full | Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study |
| title_fullStr | Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study |
| title_full_unstemmed | Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study |
| title_short | Analyzing the causal relationship between lipid-lowering drug target genes and epilepsy: a Mendelian randomization study |
| title_sort | analyzing the causal relationship between lipid lowering drug target genes and epilepsy a mendelian randomization study |
| topic | lipid-lowering medications epilepsy drug target Mendelian randomization causal genetic lipid metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1331537/full |
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