Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache

Objective Identifying common genetic variants that confer genetic risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro‐Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Annals of neurology Ročník 90; číslo 2; s. 203 - 216
Hlavní autoři: Harder, Aster V.E., Winsvold, Bendik S., Noordam, Raymond, Vijfhuizen, Lisanne S., Børte, Sigrid, Kogelman, Lisette J.A., Boer, Irene, Tronvik, Erling, Rosendaal, Frits R., Willems van Dijk, Ko, O'Connor, Emer, Fourier, Carmen, Thomas, Laurent F., Kristoffersen, Espen S., Fronczek, Rolf, Pozo‐Rosich, Patricia, Jensen, Rigmor H., Ferrari, Michel D., Hansen, Thomas F., Zwart, John‐Anker, Terwindt, Gisela M., Maagdenberg, Arn M.J.M
Médium: Journal Article
Jazyk:angličtina
Vydáno: Hoboken, USA John Wiley & Sons, Inc 01.08.2021
Wiley Subscription Services, Inc
Témata:
Blood cells
Clusters
Confidence intervals
Epidemiology
Gene expression
Gene mapping
Gene sequencing
Genetic disorders
Genetic diversity
Genetic variance
Headache
Headaches
Linkage disequilibrium
Loci
Migraine
Population studies
Ribonucleic acid
Risk
RNA
Single-nucleotide polymorphism
Statistical analysis
Tissue analysis
ISSN:0364-5134, 1531-8249, 1531-8249
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Objective Identifying common genetic variants that confer genetic risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro‐Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord‐Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell‐derived RNA‐sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11‐815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene‐based mapping yielded ASZ1 as possible fifth locus. RNA‐sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–216
Bibliografie:J.A.Z., G.M.T., and A.M.J.M.vdM. contributed equally to this work and should be considered co‐last authors.
A.V.E.H., B.S.W., and R.N. contributed equally to this work and should be considered co‐first authors.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.26146