on February 22, 2007
Published online before print February 22, 2007, doi: 10.1161/01.STR.0000260094.03782.59
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 9, 2006
From the Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine (S.I., L.W., K.I., Y.M., A.K.), Japan; Department of Neurosurgery, Takayama Red Cross Hospital (K.T.), Japan; Department of Emergency Medicine, Chunou Kousei Hospital (H.Y.), Gifu, Japan; Department of Neurosurgery, Faculty of Medicine, Saga University (M.A.), Saga, Japan; Department of Neurosurgery, New York University Medical Center (J.J.J.), New York, USA; and Stroke Center, Department of Neurology, Palacky University Medical School and University Hospital (R.H.), Olomouc, Czech Republic. * To whom correspondence should be addressed. E-mail: koizumi{at}pbh.med.kyoto-u.ac.jp.
Background and Purpose--Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background. Methods--A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program. A genome-wide association analysis of 26 cases and 30 controls was performed using a GeneChip 10K mapping array. Significance levels for linkage and single single-nucleotide polymorphism association analyses were set at P<0.05 and P<0.0001, respectively. Genotyping was also performed using 58 960 single-nucleotide polymorphisms for 2 sets of discordant twins. Results--The linkage analysis revealed 7 candidate regions, with the highest logarithm of odds score of 1.88 (P=0.002) at chromosome 6q25. A significant association was observed for 4 single-nucleotide polymorphisms and 2 haplotypes, but none of them overlapped with candidate linkage regions. Genotyping of the twins showed no genetic heterogeneity. Conclusions--The present study failed to identify genetic factors for arteriovenous malformation although the low statistical power may have resulted in such evidence being missed.
Accepted on October 30, 2006
Combination of Linkage and Association Studies for Brain Arteriovenous Malformation
Sumiko Inoue PhD;
Key words: arteriovenous malformation • association • genome-wide • genetics • linkage • microarr
This article has been cited by other articles:
 |
|
 |
|
  H. Kim, L. Pawlikowska, Y. Chen, H. Su, G.-Y. Yang, and W. L. Young Brain Arteriovenous Malformation Biology Relevant to Hemorrhage and Implication for Therapeutic Development Stroke, March 1, 2009; 40(3_suppl_1): S95 - S97. [Abstract] [Full Text] [PDF]
|
|