Related Experiment Video
Updated: Oct 17, 2025

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Phenotypic and Genotypic Associations Between Migraine and Lipoprotein Subfractions
Yanjun Guo1, Iyas Daghlas1, Padhraig Gormley1
1From 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.
Background And Objective:
To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.
Methods:
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 (ncase = 54,552, ncontrol = 297,970) and combined summary data for lipoprotein subfractions (n up to 47,713).
Results:
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 (p = 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 (chr2p21 harboring THADA, chr5q13.3 harboring HMGCR, chr6q22.31 harboring HEY2, and chr7q11.23 harboring MLXIPL) between migraine and lipoprotein subfractions. Three of these loci were replicated for migraine (p < 0.05) in a smaller sample from the UK Biobank. The shared signal at chr5q13.3 colocalized with expression of HMGCR, ANKDD1B, and COL4A3BP in multiple tissues.
Conclusions:
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.
Classification Of Evidence:
This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.
Related Concept Videos
Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
Lipid-derived Compounds in the Human Body
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
Asymmetric Lipid Bilayer
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...

