From the Division of Preventive Medicine (Y.G., I.D., F.G., P.M. Ridker, S.M., P.M. Rist, D.I.C.), Center for Cardiovascular Disease Prevention (P.M. Ridker, S.M., D.I.C.), and Center for Lipid Metabolomics (S.M.), Brigham and Women's Hospital; Harvard Medical School (Y.G., I.D., P.M. Ridker, S.M., P.M. Rist, D.I.C.); Department of Epidemiology (Y.G., T.K., P.R., D.I.C.), Harvard T.H. Chan School of Public Health; Genetics and Pharmacogenomics (P.G.), Merck & Co., Inc., Boston, MA; and Institute of Public Health (T.K.), Charité Universitätsmedizin Berlin, Germany.
Neurology. 2021 Nov 30;97(22):e2223-e2235. doi: 10.1212/WNL.0000000000012919. Epub 2021 Oct 11.
To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.
We evaluated phenotypic associations between migraine and 19 lipoprotein subfraction measures in the Women's Genome Health Study (n = 22,788). We then investigated genetic relationships between these traits using summary statistics from the International Headache Genetics Consortium for migraine (n = 54,552, n = 297,970) and combined summary data for lipoprotein subfractions (n up to 47,713).
There was a significant phenotypic association (odds ratio 1.27 [95% confidence interval 1.12-1.44]) and a significant genetic correlation at 0.18 ( = 0.001) between migraine and triglyceride-rich lipoproteins (TRLPs) concentration but not for low-density lipoprotein or high-density lipoprotein subfractions. Mendelian randomization (MR) estimates were largely null, implying that pleiotropy rather than causality underlies the genetic correlation between migraine and lipoprotein subfractions. Pleiotropy was further supported in cross-trait meta-analysis, revealing significant shared signals at 4 loci ( harboring , harboring , harboring , and harboring ) between migraine and lipoprotein subfractions. Three of these loci were replicated for migraine ( < 0.05) in a smaller sample from the UK Biobank. The shared signal at colocalized with expression of , , and in multiple tissues.
The study supports the association between certain lipoprotein subfractions, especially for TRLP, and migraine in populations of European ancestry. The corresponding shared genetic components may help identify potential targets for future migraine therapeutics.
This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.
评估偏头痛与脂蛋白亚组分之间的表型和遗传关系。
我们评估了女性基因组健康研究（n=22788）中偏头痛与 19 种脂蛋白亚组分指标之间的表型关联。然后，我们使用国际头痛遗传学联盟偏头痛的汇总统计数据（n=54552，n=297970）和脂蛋白亚组分的综合汇总数据（最多 n 为 47713），研究了这些特征之间的遗传关系。
偏头痛与富含甘油三酯的脂蛋白（TRLPs）浓度之间存在显著的表型关联（比值比 1.27[95%置信区间 1.12-1.44]）和显著的遗传相关系数为 0.18（=0.001），但与低密度脂蛋白或高密度脂蛋白亚组分无关。孟德尔随机化（MR）估计值基本为零，这表明遗传相关系数偏头痛和脂蛋白亚组分之间的关系是由多效性而不是因果关系引起的。跨特征荟萃分析进一步支持了多效性，在偏头痛和脂蛋白亚组分之间的 4 个位点（包含 、 、 、和 ）发现了显著的共享信号。其中 3 个位点在来自英国生物银行的较小样本中得到了偏头痛的复制（<0.05）。在多个组织中， 与 、 、 和 的表达共定位。
该研究支持了在欧洲裔人群中，某些脂蛋白亚组分，特别是 TRLP，与偏头痛之间的关联。相应的共享遗传成分可能有助于确定未来偏头痛治疗的潜在靶点。
本研究提供了 I 级证据，表明偏头痛与某些脂蛋白亚组分显著相关。
