PDF(Pubmed)
Abstract：
UNASSIGNED: Micronutrient levels play a critical role in epilepsy. This study investigates the impact of micronutrient levels on epilepsy via Mendelian randomization (MR).
UNASSIGNED: A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesion-negative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes.
UNASSIGNED: Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; p = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; p = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; p = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, p = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, p = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D.
UNASSIGNED: MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies.
UNASSIGNED: A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesion-negative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes.
UNASSIGNED: Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; p = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; p = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; p = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, p = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, p = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D.
UNASSIGNED: MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies.
摘要：
■微量营养素水平在癫痫中起关键作用。本研究通过孟德尔随机化（MR）调查微量营养素水平对癫痫的影响。
■双样本MR框架评估了15种血清微量营养素与癫痫表型之间的遗传关联。分析包括钙，铁,锌，硒,铜，镁，钾，叶酸,维生素B6，B12，C，D,E,视黄醇,和胡萝卜素对抗所有癫痫，全身性癫痫,儿童失神癫痫（CAE），青少年失神癫痫（JAE），青少年肌阵挛性癫痫（JME），单纯全身性强直-阵挛性癫痫发作和尖峰波脑电图（GTCS），和各种局灶性癫痫表型[与海马硬化（HS），HS以外的病变，病变阴性]。随机效应逆方差加权(IVW)模型是使用的主要方法，由异质性和多效性评估支持。多变量孟德尔随机化分析（MVMR）用于确定与不同癫痫亚型显著相关的微量营养素，并确认这些亚型的最潜在的因果危险因素。
■锌可增加HS患者发生局灶性癫痫的风险（OR=1.01；p=0.045）。胡萝卜素与病变阴性病例的高风险相似（OR=1.129；p=0.037）。相反，维生素B6与HS局灶性癫痫的风险降低相关（OR=0.949;p=0.020），维生素D与CAE(OR=0.976,95%CI:0.959-0.993,p=0.006)和JAE(OR=0.986,95%CI:0.973-0.999,p=0.032)的风险降低相关.这些协会是强大的，在各种敏感性分析中显示出最小的异质性，没有多效性的证据。使用MVMR调整后，维生素D与CAE和JAE之间存在显著的因果关系。此外，锌和维生素B6对HS局灶性癫痫的因果关系无显著意义，虽然在调整维生素D后，胡萝卜素从局灶性癫痫病灶阴性的危险因素转变为保护因素。
■MR估计提供了维生素D对降低CAE风险的因果影响的有力证据，和JAE,这可能提供替代治疗策略。
■双样本MR框架评估了15种血清微量营养素与癫痫表型之间的遗传关联。分析包括钙，铁,锌，硒,铜，镁，钾，叶酸,维生素B6，B12，C，D,E,视黄醇,和胡萝卜素对抗所有癫痫，全身性癫痫,儿童失神癫痫（CAE），青少年失神癫痫（JAE），青少年肌阵挛性癫痫（JME），单纯全身性强直-阵挛性癫痫发作和尖峰波脑电图（GTCS），和各种局灶性癫痫表型[与海马硬化（HS），HS以外的病变，病变阴性]。随机效应逆方差加权(IVW)模型是使用的主要方法，由异质性和多效性评估支持。多变量孟德尔随机化分析（MVMR）用于确定与不同癫痫亚型显著相关的微量营养素，并确认这些亚型的最潜在的因果危险因素。
■锌可增加HS患者发生局灶性癫痫的风险（OR=1.01；p=0.045）。胡萝卜素与病变阴性病例的高风险相似（OR=1.129；p=0.037）。相反，维生素B6与HS局灶性癫痫的风险降低相关（OR=0.949;p=0.020），维生素D与CAE(OR=0.976,95%CI:0.959-0.993,p=0.006)和JAE(OR=0.986,95%CI:0.973-0.999,p=0.032)的风险降低相关.这些协会是强大的，在各种敏感性分析中显示出最小的异质性，没有多效性的证据。使用MVMR调整后，维生素D与CAE和JAE之间存在显著的因果关系。此外，锌和维生素B6对HS局灶性癫痫的因果关系无显著意义，虽然在调整维生素D后，胡萝卜素从局灶性癫痫病灶阴性的危险因素转变为保护因素。
■MR估计提供了维生素D对降低CAE风险的因果影响的有力证据，和JAE,这可能提供替代治疗策略。
