Mayo Genome Consortia: A Genotype-Phenotype Resource for Genome-Wide Association Studies With an Application to the Analysis of Circulating Bilirubin Levels
Mayo Genome Consortia: A Genotype-Phenotype Resource for Genome-Wide Association Studies With an Application to the Analysis of Circulating Bilirubin Levels
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DOI：
10.4065/mcp.2011.0178
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发表时间：
2011-07-01
影响因子：
8.9
通讯作者：
Chute, Christopher G.
中科院分区：
文献类型：
--
作者：
Bielinski, Suzette J.;Chai, High Seng;Chute, Christopher G.
目的：为了创建一个具有成本效益的遗传研究队列，梅奥基因组联盟（MayoGC）汇集了来自梅奥诊所研究的参与者，他们拥有高通量遗传数据和用于表型提取的电子病历（EMR）数据。参与者和方法：符合条件的参与者包括那些在贡献研究中给予一般研究同意与其他研究者共享高通量基因分型数据的人。在此，我们描述了MayoGC的设计，包括当前参与队列，扩展工作，数据处理以及研究的管理和组织。进行了一项全基因组关联研究，以确定与总胆红素水平相关的遗传变异，以测试MayoGC的遗传研究能力。结果：尿苷5′-二磷酸葡萄糖醛酸转移酶（UGT1A）基因簇对应的2q37（单核苷酸多态性最高，rs4148325， P=5.0 × 10(-62)）和12p12（单核苷酸多态性最高，rs4363657， P=5.1 × 10(-8)）和溶质载体有机阴离子转运蛋白家族1B1 （SLC01B1）基因簇对应的12q37（单核苷酸多态性最高，rs4148325）和12p12（单核苷酸多态性最高，P=5.1 × 10(-8)）的全基因组显著性结果。结论：全基因组关联研究已经确定了与许多表型相关的遗传变异，但由于昂贵的基因分型和表型分型而受到样本量不足的限制。为了获得足够的统计能力，已经组建了具有统一基因型数据的大型联盟，但表现型仍然是基因发现研究工作中的一个限制因素。EMR包含丰富的表型数据，可以以相对快速和系统的方式提取。MayoGC为研究疾病的遗传决定因素提供了一个在共同电子病历环境下独特的合作模式。梅奥临床项目，2011；86 (7): 606 - 614
OBJECTIVE: To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with high-throughput genetic data and electronic medical record (EMR) data for phenotype extraction.PARTICIPANTS AND METHODS: Eligible participants Include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators. Herein, we describe the design of the MayoGC, Including the current participating cohorts, expansion efforts, data processing, and study management and organization. A genome-wide association study to identify genetic variants associated with total bilirubin levels was conducted to test the genetic research capability of the MayoGC.RESULTS: Genome-wide significant results were observed on 2q37 (top single nucleotide polymorphism, rs4148325; P=5.0 x 10(-62)) and 12p12 (top single nucleotide polymorphism, rs4363657; P=5.1 x 10(-8)) corresponding to a gene cluster of uridine 5'-diphospho-glucuronosyltransferases (the UGT1A cluster) and solute carrier organic anion transporter family, member 1B1 (SLC01B1), respectively.CONCLUSION: Genome-wide association studies have identified genetic variants associated with numerous phenotypes but have been historically limited by inadequate sample size due to costly genotyping and phenotyping. Large consortia with harmonized genotype data have been assembled to attain sufficient statistical power, but phenotyping remains a rate-limiting factor in gene discovery research efforts. The EMR consists of an abundance of phenotype data that can be extracted in a relatively quick and systematic manner. The MayoGC provides a model of a unique collaborative effort in the environment of a common EMR for the investigation of genetic determinants of diseases. Mayo Clin Proc. 2011;86(7):606-614