Combination of linkage and association studies for brain arteriovenous malformation
Combination of linkage and association studies for brain arteriovenous malformation
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DOI：
10.1161/01.str.0000260094.03782.59
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发表时间：
2007-04-01
期刊：
影响因子：
8.3
通讯作者：
Koizumi, Akio
中科院分区：
文献类型：
--
作者：
Inoue, Sumiko;Liu, Wanyang;Koizumi, Akio
背景与目的：脑动静脉畸形的遗传因素尚不清楚，因为家族性病例的发生率较低，尽管存在局部和家族聚集性。我们采用连锁研究和关联研究相结合的方法来探索遗传背景。方法：使用GENEHUNTER程序对来自6个无亲缘关系家庭的12例患者进行全基因组连锁分析。使用GeneChip 10K定位阵列对26例病例和30例对照进行全基因组关联分析。连锁和单核苷酸多态性关联分析的显著性水平分别为P < 0.05和P < 0.0001。对2对异卵双胞胎进行58 960个单核苷酸多态性基因分型。结果：连锁分析共发现7个候选区域，在6q25染色体上的对数优势值最高，为1.88 （P = 0.002）。4个单核苷酸多态性和2个单倍型均与候选连锁区无重叠。这对双胞胎的基因分型显示没有遗传异质性。结论：本研究未能确定动静脉畸形的遗传因素，尽管低统计力可能导致这些证据被遗漏。
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.