Merck Research Laboratories, Boston, MA 02115, USA.
Genome Res. 2011 Jul;21(7):1008-16. doi: 10.1101/gr.112821.110. Epub 2011 May 20.
To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1000 patients undergoing Roux-en-Y gastric bypass (RYGB) and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than 100,000 gene expression traits representing four metabolically relevant tissues: liver, omental adipose, subcutaneous adipose, and stomach. We successfully identified 24,531 eSNPs corresponding to about 10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high-quality disease map for each tissue in morbidly obese patients to not only inform genetic associations identified in this cohort, but in previously published genome-wide association studies as well. These data can aid in elucidating the key networks associated with morbid obesity, response to RYGB, and disease as a whole.
为了绘制与代谢相关组织中基因表达的遗传学图谱,并研究来自同一个体的多个组织中表达单核苷酸多态性(eSNP)的多样性,我们从接受 Roux-en-Y 胃旁路术(RYGB)的约 1000 名患者中收集了四个组织,并收集了与他们的体重减轻和合并症相关的临床特征。然后,我们进行了高通量基因分型和基因表达谱分析,并对代表四个与代谢相关的组织(肝脏、网膜脂肪、皮下脂肪和胃)的超过 100,000 个基因表达特征进行了全基因组关联分析。我们成功鉴定了 24,531 个 eSNP,对应约 10,000 个不同的基因。这代表了迄今为止任何研究中鉴定出的 eSNP 数量最多的一次,也是首次从胃组织中鉴定出 eSNP 的研究。然后,我们展示了这些 eSNP 如何为病态肥胖患者的每个组织提供高质量的疾病图谱,不仅可以为该队列中鉴定的遗传关联提供信息,还可以为之前发表的全基因组关联研究提供信息。这些数据可以帮助阐明与病态肥胖、RYGB 反应以及整个疾病相关的关键网络。