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Cephalalgia. 2016 Jun;36(7):604-14. doi: 10.1177/0333102414566820. Epub 2015 Jan 29.

Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set.

Author information

1
Department of Human Genetics, Leiden University Medical Center, the Netherlands.
2
Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Harvard Medical School, USA Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, USA.
3
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany.
4
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Institute of Genetics, Folkhälsan Research Center, Finland.
5
Department of Neurology, Helsinki University Central Hospital, Finland.
6
Kiel Pain and Headache Center, Germany.
7
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
8
Institute of Human Genetics, University of Ulm, Germany.
9
Department of Neurology, Leiden University Medical Center, the Netherlands.
10
Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Stanley Center for Psychiatric Research, Broad Institute for Harvard and MIT, USA Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Psychiatric and Neurodevelopmental Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Department of Neurology, Massachusetts General Hospital, USA.
11
Department of Neurology, Leiden University Medical Center, the Netherlands G.M.Terwindt@lumc.nl.
12
Department of Human Genetics, Leiden University Medical Center, the Netherlands Department of Neurology, Leiden University Medical Center, the Netherlands.

Abstract

BACKGROUND:

Before the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set.

METHODS:

We selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500 kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls.

RESULTS:

None of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately.

CONCLUSION:

The available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine.

KEYWORDS:

GWAS data; Migraine; SNP; candidate genes

PMID:
25633374
DOI:
10.1177/0333102414566820
[Indexed for MEDLINE]

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