| Title: | Phenotypic and Genotypic Associations Between Migraine and Lipoprotein Subfractions |
| Journal: | Neurology |
| Published: | 11 Oct 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34635557/ |
| DOI: | https://doi.org/10.1212/wnl.0000000000012919 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641972 |
| Citations: | 12 (11 in last 2 years) as of 8 Aug 2024 |
Publication 12672
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND AND OBJECTIVE: To evaluate phenotypic and genetic relationships between migraine and lipoprotein subfractions.</p>
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).</p>
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.</p>
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.</p>
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that migraine is significantly associated with some lipoprotein subfractions.</p>
7 Keywords
- Female
- Genome-Wide Association Study
- Genotype
- Humans
- Lipoproteins
- Migraine Disorders
- Phenotype
9 Authors
- Yanjun Guo
- Iyas Daghlas
- Padhraig Gormley
- Franco Giulianini
- Paul M Ridker
- Samia Mora
- Tobias Kurth
- Pamela M Rist
- Daniel I Chasman
1 Application
| Application ID | Title |
|---|---|
| 29273 | Genetic analysis of peripheral artery disease and migraine |
Enabling scientific discoveries that improve human health