gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

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Genome-wide association analysis of Caucasian Moyamoya patients identifies four highly significant risk loci

Meeting Abstract

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  • Constantin Roder - Klinik für Neurochirurgie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Markus Krämer - Klinik für Neurologie, Alfried-Krupp-von Bohlen und Halbach Krankenhaus Essen, Essen, Deutschland
  • Nadia Khan - Klinik für Neurochirurgie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland; Kinderspital Zürich, Universitäts-Kinderkliniken Zürich, Schweiz
  • Marcos Tatagiba - Klinik für Neurochirurgie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Akio Koizumi - Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo, Kyoto, Japan
  • Boris Krischek - Klinik für Neurochirurgie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMO.13.06

doi: 10.3205/13dgnc111, urn:nbn:de:0183-13dgnc1119

Published: May 21, 2013

© 2013 Roder et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective: Moyamoya Disease (MMD) is defined by changes of major intracranial vessels consisting of a stenosis and surrounding collaterals. Recent research shows that genetics very likely play a major role in the idiopathic and familial forms of this disease. However, the rareness of this disease, possible differences between ethnicities and a possible multi-factorial genesis complicate the identification of disease-causing genes.

Method: Genome-wide association analysis (GWAS) of 576.736 single nucleotide polymorphisms (SNPs) comparing 38 Caucasian MMD patients and 42 healthy controls was performed. Significant results with p<0.00005 were included in a combined analysis with HapMap CEU genotyping data

Results: The combined analysis of GWAS results and HapMap CEU genotyping data revealed strong association of 5 SNPs (rs7546890, rs716218, rs1030483, rs1340932, rs6044710) in or adjacent to 4 genes (F11R, MEIS2, CALB2, PCSK2) with p-values <0.00005. The strongest association was found for rs7546890, located in intron 1 of the F11R gene on Chromosome 1q21.2-q21.3, with a p value of 4.10E-14, OR 7.22, 95% CI 4.15-12.57.

Conclusions: GWAS of 576.736 SNPs in Caucasian MMD samples revealed 4 new candidate genes (F11R, MEIS2, CALB2, PCSK2) for the genesis of this disease. Strongest disease association was found for F11R. The literature suggests possible MMD-causing pathomechanisms related to F11R: activation of platelets and endothelial surfaces could lead to stenotic changes of vessels as seen in Moyamoya Disease. Further analysis of this gene might lead to a better understanding of the etiology of MMD, as well as differences between Asian and Caucasian disease forms. Such findings might have implications on diagnosis and treatment of Moyamoya Disease.