Search for intracranial aneurysm susceptibility gene(s) using Finnish families.
Search for intracranial aneurysm susceptibility gene(s) using Finnish families.
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使用芬兰家庭搜索颅内动脉瘤敏感性基因。
DOI：
10.1186/1471-2350-3-7
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发表时间：
2002-08-01
影响因子：
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通讯作者：
Tromp, Gerard
中科院分区：
文献类型：
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作者：
Olson, Jane M;Vongpunsawad, Sompong;Kuivaniemi, Helena;Ronkainen, Antti;Hernesniemi, Juha;Ryynanen, Markku;Kim, Lee-Lian;Tromp, Gerard
脑血管疾病是美国第三大死亡原因，约四分之一的脑血管死亡归因于颅内动脉瘤破裂（IA）。流行病学证据表明，IA在家庭中聚集，因此可能是遗传的。通过基因检测识别有患IA风险的个体将使诊断成像集中在高风险个体上。我们使用无模型连锁分析的基础上等位基因共享与两阶段设计的全基因组扫描，以确定染色体区域，可能窝藏IA基因座。我们先前估计芬兰人群中兄弟姐妹的相对风险在9到16岁之间，并继续进行全基因组扫描以寻找易患IA的基因座。在85个有两个或更多受影响成员的芬兰家庭中，有48个受影响的兄弟姐妹对（ASP）可用于我们的遗传研究。功效计算表明，48个ASP足以鉴定可能含有易感基因的染色体区域，并且0.8的自由I期lod评分阈值提供了假阳性区域检测和未能检测到具有中等效果的真实的位点之间的合理平衡。7个染色体区域超过了I期lod评分阈值0.8，5个超过了1.0。最重要的区域，在染色体19 q上，有一个最大的多点lod得分（MLS）为2.6。我们的研究为IA易感基因的定位提供了证据。进一步的研究是必要的，以阐明基因及其在IA的病理生理学中的作用，并设计遗传检测。
Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci. We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect. Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6. Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.