Jeff Janina M, Armstrong Loren L, Ritchie Marylyn D, Denny Joshua C, Kho Abel N, Basford Melissa A, Wolf Wendy A, Pacheco Jennifer A, Li Rongling, Chisholm Rex L, Roden Dan M, Hayes M Geoffrey, Crawford Dana C
Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, Vanderbilt University, Nashville, Tennessee, United States of America.
Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
PLoS One. 2014 Mar 3;9(3):e86931. doi: 10.1371/journal.pone.0086931. eCollection 2014.
Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Genome-wide association studies (GWAS) have identified several loci that contribute to T2D in European Americans, but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in this African American dataset. We were unable to identify novel associations at p<5.0×10(-8) by GWAS. Using admixture mapping as an alternative method for discovery, we performed a genome-wide admixture scan that suggests multiple candidate genes associated with T2D. One finding, TCIRG1, is a T-cell immune regulator expressed in the pancreas and liver that has not been previously implicated for T2D. We performed subsequent fine-mapping to further assess the association between TCIRG1 and T2D in >5,000 African Americans. We identified 13 independent associations between TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11 and T2D. Our results suggest a novel region on chromosome 11 identified by admixture mapping is associated with T2D in African Americans.
2型糖尿病（T2D）是一种复杂的代谢性疾病，对非裔美国人的影响尤为严重。全基因组关联研究（GWAS）已经确定了几个导致欧裔美国人患T2D的基因座，但在混合人群中进行的研究却很少。作为电子病历与基因组学（eMERGE）网络的一部分，我们首先对来自范德比尔特基因组-电子记录项目和西北大学NUgene项目的1563名非裔美国人进行了GWAS。我们成功地在TCF7L2中复制了一种关联，该关联此前已在这个非裔美国人数据集中通过GWAS确定。通过GWAS，我们无法在p<5.0×10(-8)的水平上识别出新的关联。作为一种替代发现方法，我们使用混合映射进行了全基因组混合扫描，结果表明有多个与T2D相关的候选基因。其中一个发现是TCIRG1，它是一种在胰腺和肝脏中表达的T细胞免疫调节因子，此前尚未被认为与T2D有关。我们随后进行了精细定位，以进一步评估在5000多名非裔美国人中TCIRG1与T2D之间的关联。我们在11号染色体上的TCIRG1、CHKA和ALDH3B1基因与T2D之间确定了13个独立的关联。我们的结果表明，通过混合映射确定的11号染色体上的一个新区域与非裔美国人的T2D有关。
