Genetic epidemiology: successes and challenges of genome-wide association studies using the example of age-related macular degeneration.
Genetic epidemiology: successes and challenges of genome-wide association studies using the example of age-related macular degeneration.
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DOI：
10.1016/j.ajo.2010.06.012
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发表时间：
2010-10
影响因子：
4.2
通讯作者：
Seddon, Johanna M.
中科院分区：
文献类型：
--
作者：
Peter, Inga;Seddon, Johanna M.
随着越来越多的证据表明遗传因素和基因-环境相互作用在常见眼科疾病的病因中的重要性，识别与疾病风险相关的基因变异可能有助于深入了解疾病的发病机制，并为预防和治疗干预提供新的靶点。基于家族的研究已经确定了与与罕见的家族性眼病相关的高渗透性基因相关的基因组区域。然而，晚发性复杂表型，如年龄相关性黄斑变性(AMD)，似乎是多基因的，涉及多个基因，影响程度各不相同。据估计，人类约90%的序列变异是DNA单碱基的差异，称为单核苷酸多态(SNPs)。根据数据库SNP(可在http://www.获得国家调查局。NLM。美国国立卫生研究院。GOV/PROJECTS/SNP)，已经确定了1400多万个唯一映射的SNPs，并将其汇编到一个全基因组数据库中。HapMap工作(可在http://hapmap.上获得Org)使得检查整个基因组所需的SNPs的数量减少到大约100万个代表性的SNPs，也被称为标记SNPs，使得将基因与疾病风险联系起来的全基因组方法更有效，成本更低。在过去的几年里，全基因组关联研究(GWAS)被设计用来评估性状和分布在基因组上的大量DNA序列变异之间的关联，并使用一种无偏见的无假设的方法来发现与疾病相关的新途径。基于疾病发病机制的常见变异-常见疾病假说，GWAS旨在识别等位基因频率为5%的常见SNPs，这些SNPs可能仅适度增加疾病风险。目前，http://www.已报告和编目了606个GWAs基因组。政府/政府。仅在过去的两年里，就已经确定了250多个遗传位点，其中常见的变异与一些多基因性状可重复地关联。1然而，尽管全球气候变化框架取得了重大成功，但它们之间的不一致是公认的限制。
WITH INCREASING EVIDENCE OF IMPORTANCE OF genetic factors and gene-environment interactions in the etiology of common eye-related disorders, identification of genetic variation associated with a disease risk may help provide insight into the mechanism of disease pathogenesis and reveal novel targets for preventive and therapeutic interventions. Familybased studies have identified genomic regions associated with highly penetrant genes related to rare familial forms of eye diseases. However, late-onset complex phenotypes, such as age-related macular degeneration (AMD), appear to be polygenic, with the involvement of multiple genes, with varying levels of effect. It has been estimated that about 90% of sequence variants in humans are differences in single bases of DNA, called single nucleotide polymorphisms (SNPs). According to dbSNP (available at http://www. ncbi. nlm. nih. gov/projects/SNP), more than 14 million uniquely mapped SNPs have been identified and assembled into a genomewide database. The HapMap effort (available at http://hapmap. org) allowed reducing the number of SNPs required for the examination of the entire genome to roughly a million representative SNPs, also called tagging SNPs, making genome-wide approaches to associate genes with risk of diseases more efficient and less costly. During the past several years, genome-wide association studies (GWAS) have been designed to assess associations between traits and a large number of DNA sequence variants distributed across the genome, and to detect novel disease-associated pathways using an unbiased hypothesis-free approach. Based on the common variant-common disease hypothesis of disease pathogenesis, GWAS are aimed at identifying common SNPs with allele frequency of 5% that may only modestly increase the disease risk. Currently, 606 GWAS have been reported and catalogued at http://www. genome. gov/gwastudies. More than 250 genetic loci in which common variants were reproducibly associated with a number of polygenic traits have been identified during the last 2 years only. 1 However, despite significant successes achieved by GWAS, their inconsistency is a generally recognized limitation.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
5.2
作者：
Fagerness, Jesen A.;Maller, Julian B.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.
影响因子：
4.4
作者：
Seddon JM;Reynolds R;Maller J;Fagerness JA;Daly MJ;Rosner B
通讯作者：
Rosner B
影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
Maller, Julian B.;Fagerness, Jesen A.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.