HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study.
Humans
Mendelian Randomization Analysis
Hydroxymethylglutaryl CoA Reductases
/ genetics
Migraine Disorders
/ genetics
Genome-Wide Association Study
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Genetic Predisposition to Disease
HMG-CoA reductase
Mendelian randomization
Migraine
Statins
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 May 2024
27 May 2024
Historique:
received:
21
11
2023
accepted:
07
05
2024
medline:
28
5
2024
pubmed:
28
5
2024
entrez:
27
5
2024
Statut:
epublish
Résumé
Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30-1.84, P = 6.87 × 10
Identifiants
pubmed: 38802400
doi: 10.1038/s41598-024-61628-9
pii: 10.1038/s41598-024-61628-9
doi:
Substances chimiques
Hydroxymethylglutaryl CoA Reductases
EC 1.1.1.-
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
12094Subventions
Organisme : National Natural Science Foundation of China
ID : Grant No. 31872772
Organisme : Natural Science Foundation of Jilin Province of China
ID : Grant No. 20200201606JC
Investigateurs
Aarno Palotie
(A)
Alice Pressman
(A)
Andrea C Belin
(AC)
Anna Bjornsdottir
(A)
Arn M J M van den Maagdenberg
(AMJM)
Aster V E Harder
(AVE)
Bendik S Winsvold
(BS)
Bertram Müller-Myhsok
(B)
Bru Cormand
(B)
Caroline Ran
(C)
Carrie Northover
(C)
Christian Kubisch
(C)
Cornelia van Duijn
(C)
Dale R Nyholt
(DR)
Daniel I Chasman
(DI)
Danielle Posthuma
(D)
Davor Lessel
(D)
Dorret I Boomsma
(DI)
Eija Hämäläinen
(E)
Espen S Kristoffersen
(ES)
Ester Cuenca-Leon
(E)
George Davey-Smith
(G)
Gisela M Terwindt
(GM)
Gudrun R Sigurdardottir
(GR)
Gyda Bjornsdottir
(G)
Heidi Hautakangas
(H)
Hreinn Stefansson
(H)
Irene de Boer
(I)
Jaakko Kaprio
(J)
Jes Olesen
(J)
John-Anker Zwart
(JA)
Kari Stefansson
(K)
Lannie Ligthart
(L)
Lenore Launer
(L)
Linda M Pedersen
(LM)
Lisette J A Kogelman
(LJA)
Lyn R Griffiths
(LR)
M Arfan Ikram
(MA)
Maija Wessman
(M)
Mari Kaunisto
(M)
Maria G Hrafnsdottir
(MG)
Marjo Hiekkala
(M)
Marjo-Riitta Järvelin
(MR)
Martin Dichgans
(M)
Matti Pirinen
(M)
Mikko Kallela
(M)
Mitja Kurki
(M)
Mona A Chalmer
(MA)
Nancy Pedersen
(N)
Olafur A Sveinsson
(OA)
Olli Raitakari
(O)
Padhraig Gormley
(P)
Patricia Pozo-Rosich
(P)
Priit Palta
(P)
Rainer Malik
(R)
Risto Kajanne
(R)
Sigrid Børte
(S)
Sigurdur H Magnusson
(SH)
Terho Lehtimäki
(T)
Thomas F Hansen
(TF)
Thorgeir E Thorgeirsson
(TE)
Tobias Freilinger
(T)
Tobias Kurth
(T)
Tonu Esko
(T)
Verneri Anttila
(V)
Ville Artto
(V)
Informations de copyright
© 2024. The Author(s).
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