A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility.
A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility.
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DOI：
10.1007/s10048-012-0325-x
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发表时间：
2012-08
期刊：
影响因子：
2.2
通讯作者：
Griffiths, Lyn R.
中科院分区：
文献类型：
--
作者：
Cox, Hannah C.;Lea, Rod A.;Bellis, Claire;Carless, Melanie;Dyer, Thomas D.;Curran, Joanne;Charlesworth, Jac;Macgregor, Stuart;Nyholt, Dale;Chasman, Daniel;Ridker, Paul M.;Schuerks, Markus;Blangero, John;Griffiths, Lyn R.
偏头痛是一种常见的神经系统疾病，具有复杂的遗传病因。该疾病影响约12%的高加索人口，女性被诊断的可能性是男性的三倍。为了确定与偏头痛易感性相关的基因位点，我们对偏头痛高发的诺福克岛孤立人群进行了一项基于家系的全基因组关联研究。这个独特的种群起源于少数英国和波利尼西亚的创始人，他们是邦蒂兵变的后代，形成了一个非常大的多代谱系（Bellis et al.; Human Genetics, 124(5): 543-5542, 2008）。这些群体遗传特征可能有助于疾病基因定位策略(Peltonen et .；生物医学进展，1(3):182 - 90,2000。在这项研究中，我们发现偏头痛在诺福克岛人群中具有高遗传率（h2=0.53， P=0.016）。我们进行了一个基于谱系的GWAS，并利用统计和病理优先排序方法来暗示偏头痛的一些变异。位于锌指蛋白555 （ZNF555）基因（rs4807347）的SNP在我们的诺福克岛家系（P=9.6×10−6）中显示了统计学相关性（P=9.6×10−6），并且在一个与bbb500偏头痛患者无关的大型独立队列中也有复制。此外，我们利用生物学优先级来暗示四个SNP，在ADARB2基因内，GRM7基因内的两个SNP和靠近HTR7基因的单个SNP。这些神经递质相关基因内的单核苷酸多态性表明，可能是诺福克岛谱系特有的5 -羟色胺能系统被破坏，但这可能为更普遍地理解偏头痛提供线索。
Migraine is a common neurological disease with a complex genetic aetiology. The disease affects ~12% of the Caucasian population and females are three times more likely than males to be diagnosed. In an effort to identify loci involved in migraine susceptibility, we performed a pedigree-based genome-wide association study of the isolated population of Norfolk Island, which has a high prevalence of migraine. This unique population originates from a small number of British and Polynesian founders who are descendents of the Bounty mutiny and forms a very large multigenerational pedigree (Bellis et al.; Human Genetics, 124(5):543–5542, 2008). These population genetic features may facilitate disease gene mapping strategies (Peltonen et al.; Nat Rev Genet, 1(3):182–90, 2000. In this study, we identified a high heritability of migraine in the Norfolk Island population (h2=0.53, P=0.016). We performed a pedigree-based GWAS and utilised a statistical and pathological prioritisation approach to implicate a number of variants in migraine. An SNP located in the zinc finger protein 555 (ZNF555) gene (rs4807347) showed evidence of statistical association in our Norfolk Island pedigree (P=9.6×10−6) as well as replication in a large independent and unrelated cohort with >500 migraineurs. In addition, we utilised a biological prioritisation to implicate four SNPs, in within the ADARB2 gene, two SNPs within the GRM7 gene and a single SNP in close proximity to a HTR7 gene. Association of SNPs within these neurotransmitter-related genes suggests a disrupted serotoninergic system that is perhaps specific to the Norfolk Island pedigree, but that might provide clues to understanding migraine more generally.
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影响因子：
120.7
作者：
Kurth, Tobias;Gaziano, J. Michael;Buring, Julie E.
通讯作者：
Buring, Julie E.
影响因子：
9.9
作者：
Lipton, R. B.;Bigal, M. E.;Stewart, W. F.
通讯作者：
Stewart, W. F.
影响因子：
30.8
作者：
De Fusco, M;Marconi, R;Casari, G
通讯作者：
Casari, G
DOI：
10.1375/twin.6.5.422
发表时间：
2003-10-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Mulder, EJ;van Baal, C;Palotie, A
通讯作者：
Palotie, A
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.