The availability of genome-wide association studies (GWASs) for human blood metabolome provides an excellent opportunity for studying metabolism in a heritable disease such as migraine. Utilizing GWAS summary statistics, we conduct comprehensive pairwise genetic analyses to estimate polygenic genetic overlap and causality between 316 unique blood metabolite levels and migraine risk. We find significant genome-wide genetic overlap between migraine and 44 metabolites, mostly lipid and organic acid metabolic traits (FDR < 0.05). We also identify 36 metabolites, mostly related to lipoproteins, that have shared genetic influences with migraine at eight independent genomic loci (posterior probability > 0.9) across chromosomes 3, 5, 6, 9, and 16. The observed relationships between genetic factors influencing blood metabolite levels and genetic risk for migraine suggest an alteration of metabolite levels in individuals with migraine. Our analyses suggest higher levels of fatty acids, except docosahexaenoic acid (DHA), a very long-chain omega-3, in individuals with migraine. Consistently, we found a causally protective role for a longer length of fatty acids against migraine. We also identified a causal effect for a higher level of a lysophosphatidylethanolamine, LPE(20:4), on migraine, thus introducing LPE(20:4) as a potential therapeutic target for migraine.

人类血液代谢组的全基因组关联研究 (GWAS) 的可用性为研究偏头痛等遗传性疾病的代谢提供了极好的机会。利用 GWAS 汇总统计数据，我们进行了全面的成对遗传分析，以估计 316 种独特的血液代谢物水平与偏头痛风险之间的多基因遗传重叠和因果关系。我们发现偏头痛和 44 种代谢物之间存在显着的全基因组遗传重叠，主要是脂质和有机酸代谢特征（FDR < 0.05）。我们还鉴定了 36 种代谢物，主要与脂蛋白相关，它们在 3、5、6、9 和 16 号染色体的 8 个独立基因组位点（后验概率 > 0.9）与偏头痛具有共同的遗传影响。观察到影响血液代谢物水平的遗传因素与偏头痛遗传风险之间的关系表明，偏头痛患者的代谢物水平发生了变化。我们的分析表明，偏头痛患者体内的脂肪酸含量较高，除了二十二碳六烯酸 (DHA)，一种非常长的链 omega-3。一致地，我们发现更长的脂肪酸对偏头痛具有因果保护作用。我们还确定了较高水平的溶血磷脂酰乙醇胺 LPE(20:4) 对偏头痛的因果影响，因此将 LPE(20:4) 作为偏头痛的潜在治疗靶点。一致地，我们发现更长的脂肪酸对偏头痛具有因果保护作用。我们还确定了较高水平的溶血磷脂酰乙醇胺 LPE(20:4) 对偏头痛的因果影响，因此将 LPE(20:4) 作为偏头痛的潜在治疗靶点。一致地，我们发现更长的脂肪酸对偏头痛具有因果保护作用。我们还确定了较高水平的溶血磷脂酰乙醇胺 LPE(20:4) 对偏头痛的因果影响，因此将 LPE(20:4) 作为偏头痛的潜在治疗靶点。