Candidate gene association resource (CARe): design, methods, and proof of concept.
Candidate gene association resource (CARe): design, methods, and proof of concept.
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DOI：
10.1161/circgenetics.109.882696
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发表时间：
2010-06
期刊：
影响因子：
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通讯作者：
NHLBI Candidate Gene Association Resource
中科院分区：
文献类型：
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作者：
Musunuru K;Lettre G;Young T;Farlow DN;Pirruccello JP;Ejebe KG;Keating BJ;Yang Q;Chen MH;Lapchyk N;Crenshaw A;Ziaugra L;Rachupka A;Benjamin EJ;Cupples LA;Fornage M;Fox ER;Heckbert SR;Hirschhorn JN;Newton-Cheh C;Nizzari MM;Paltoo DN;Papanicolaou GJ;Patel SR;Psaty BM;Rader DJ;Redline S;Rich SS;Rotter JI;Taylor HA Jr;Tracy RP;Vasan RS;Wilson JG;Kathiresan S;Fabsitz RR;Boerwinkle E;Gabriel SB;NHLBI Candidate Gene Association Resource
.国家心脏，肺和血液研究所的候选基因协会资源（CARe）是一项计划中的心血管，肺，血液学和睡眠相关性状遗传变异的跨队列分析，包括超过40，000名参与者，代表九个社区队列中的四个种族。CARe的目标包括使用候选基因方法发现与性状相关的新变体，以及使用全基因组关联映射方法发现新变体，特别是在非洲裔美国人中。. CARe已经收集了超过40，000名自认为是欧洲裔美国人，非洲裔美国人，西班牙裔美国人或华裔美国人的DNA样本，并附带了数百种表型的数据，这些表型已被标准化并保存在CARe表型数据库中。所有参与者的基因分型为七个单核苷酸多态性（SNPs）的基础上选择先前的关联证据。我们进行了关联分析，将这些SNP中的每一个与脂质性状相关，按性别和种族分层，并根据年龄和年龄进行调整。在至少两个种族中，CETP、LIPC和LPL附近的SNP与高密度脂蛋白胆固醇浓度、PCSK 9与低密度脂蛋白胆固醇水平以及LPL和APOA 5与血清甘油三酯密切相关。值得注意的是，一些SNP在不同种族群体中显示出不同的效应大小和关联意义。. CARe试点研究验证了CARe项目的表型收集、SNP基因分型和分析管道的操作框架，并验证了计划在所有参与者中进行的约2，000个生物候选基因座的候选基因研究和在约8，000名非洲裔美国人参与者中进行的全基因组关联研究。CARe将成为科学界的宝贵资源。
. The National Heart, Lung, and Blood Institute’s Candidate Gene Association Resource (CARe), a planned cross-cohort analysis of genetic variation in cardiovascular, pulmonary, hematological, and sleep-related traits, comprises more than 40,000 participants representing four ethnic groups in nine community-based cohorts. The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans. . CARe has assembled DNA samples for more than 40,000 individuals self-identified as European-American, African-American, Hispanic, or Chinese-American, with accompanying data on hundreds of phenotypes that have been standardized and deposited in the CARe Phenotype Database. All participants were genotyped for seven single-nucleotide polymorphisms (SNPs) selected based on prior association evidence. We performed association analyses relating each of these SNPs to lipid traits, stratified by gender and ethnicity and adjusted for age and age. In at least two of the ethnic groups, SNPs near CETP, LIPC, and LPL strongly replicated for association with high-density lipoprotein cholesterol concentrations, PCSK9 with low-density lipoprotein cholesterol levels, and LPL and APOA5 with serum triglycerides. Notably, some SNPs showed varying effect sizes and significance of association in different ethnic groups. . The CARe Pilot Study validates the operational framework for phenotype collection, SNP genotyping, and analytical pipeline of the CARe project and validates the planned candidate gene study of ~2,000 biologic candidate loci in all participants and genome-wide association study in ~8,000 African-American participants. CARe will serve as a valuable resource for the scientific community.