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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

机译：CNV的全基因组关联研究涉及16,000例八种常见疾病和3,000个共享控制

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Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed ～19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated ～50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
机译：拷贝数变异（CNV）在人类遗传多态性中占很大比例，据预测在常见疾病的遗传易感性中具有重要作用。为了解决这个问题，我们进行了一项大型，直接的全基因组研究，研究了CNV与八种常见人类疾病之间的关联。使用专门设计的阵列，我们在3,432个多态CNV上将约19,000个个体分为不同的拷贝数类别，其中包括约500％大于500个碱基对的所有常见CNV。我们鉴定了几种导致假阳性关联的生物制品，包括从血液和细胞系衍生的DNA之间的系统CNV差异。关联测试和后续复制分析证实了三个基因座，其中CNV与克罗恩氏病相关-IRGM，克罗恩氏病，类风湿性关节炎和1型糖尿病的HLA，以及2型糖尿病的TSPAN8-尽管在每种情况下，以前在基于单核苷酸多态性（SNP）的研究中已鉴定出SNP，这反映了我们的观察结果，即在阵列上正确键入的大多数常见CNV均已被SNP很好地标记，因此已通过SNP研究进行了间接探索。我们得出的结论是，可以在现有平台上键入的常见CNV不太可能对常见人类疾病的遗传基础做出重大贡献。

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    《Nature》 |2010年第7289期|713-720|共8页
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  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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