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Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

ABSTRACT: Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10??, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10?¹¹ (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10??, permuted threshold for genome-wide significance 7.7 × 10??. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

SUBMITTER: Anttila V

PROVIDER: S-EPMC2948563 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

Anttila Verneri V Stefansson Hreinn H Kallela Mikko M Todt Unda U Terwindt Gisela M GM Calafato M Stella MS Nyholt Dale R DR Dimas Antigone S AS Freilinger Tobias T Müller-Myhsok Bertram B Artto Ville V Inouye Michael M Alakurtti Kirsi K Kaunisto Mari A MA Hämäläinen Eija E de Vries Boukje B Stam Anine H AH Weller Claudia M CM Heinze Axel A Heinze-Kuhn Katja K Goebel Ingrid I Borck Guntram G Göbel Hartmut H Steinberg Stacy S Wolf Christiane C Björnsson Asgeir A Gudmundsson Gretar G Kirchmann Malene M Hauge Anne A Werge Thomas T Schoenen Jean J Eriksson Johan G JG Hagen Knut K Stovner Lars L Wichmann H-Erich HE Meitinger Thomas T Alexander Michael M Moebus Susanne S Schreiber Stefan S Aulchenko Yurii S YS Breteler Monique M B MM Uitterlinden Andre G AG Hofman Albert A van Duijn Cornelia M CM Tikka-Kleemola Päivi P Vepsäläinen Salli S Lucae Susanne S Tozzi Federica F Muglia Pierandrea P Barrett Jeffrey J Kaprio Jaakko J Färkkilä Markus M Peltonen Leena L Stefansson Kari K Zwart John-Anker JA Ferrari Michel D MD Olesen Jes J Daly Mark M Wessman Maija M van den Maagdenberg Arn M J M AM Dichgans Martin M Kubisch Christian C Dermitzakis Emmanouil T ET Frants Rune R RR Palotie Aarno A

Nature genetics 20100829 10

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10⁻⁹, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three Europ ...[more]

PMID: 20802479

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Project description:Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk.We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10(-7) by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18-1.51], 1.24 (95% CI, 1.14-1.35), 1.28 (95% CI, 1.17-1.40), and 1.26 (95% CI, 1.15-1.38), respectively, for lung cancer risk.Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer.To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk.

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Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

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Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

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