在 GENNID 研究的非裔美国人亚组中，每个连锁区域都包含多个 2 型糖尿病基因。
Five linkage regions each harbor multiple type 2 diabetes genes in the African American subset of the GENNID Study.
机构信息
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112 5330, USA.
出版信息
J Hum Genet. 2013 Jun;58(6):378-83. doi: 10.1038/jhg.2013.21. Epub 2013 Apr 4.
Abstract
We previously localized type 2 diabetes (T2D)-susceptibility genes to five chromosomal regions through a genome-wide linkage scan of T2D and age of diagnosis (AOD) in the African American subset of the GENNID sample. To follow up these findings, we repeated the linkage and association analysis using genotypes on an additional 9203 fine-mapping single nucleotide polymorphisms (SNPs) selected to tag genes under the linkage peaks. In each of the five regions, we confirmed linkage and inferred the presence of ≥2 susceptibility genes. The evidence of multiple susceptibility genes consisted of: (1) multiple linkage peaks in four of the five regions; and (2) association of T2D and AOD with SNPs within ≥2 genes in every region. The associated genes included 3 previously reported to associate with T2D or related traits (GRB10, NEDD4L, LIPG) and 24 novel candidate genes, including genes in lipid metabolism (ACOXL) and cell-cell and cell-matrix adhesion (MAGI2, CLDN4, CTNNA2).
摘要
我们之前通过对 GENNID 样本中非洲裔美国人亚组的 2 型糖尿病（T2D）和诊断年龄（AOD）进行全基因组连锁扫描，将 T2D 易感性基因定位于五个染色体区域。为了跟进这些发现，我们使用连锁峰下选择的另外 9203 个精细映射单核苷酸多态性（SNP）的基因型重复了连锁和关联分析。在五个区域中的每一个区域，我们都确认了连锁，并推断出存在≥2 个易感基因。多个易感基因的证据包括：（1）五个区域中的四个区域存在多个连锁峰；（2）T2D 和 AOD 与每个区域中≥2 个基因内的 SNP 相关。相关基因包括 3 个先前报道与 T2D 或相关特征相关的基因（GRB10、NEDD4L、LIPG）和 24 个新的候选基因，包括脂质代谢（ACOXL）和细胞-细胞和细胞-基质粘附（MAGI2、CLDN4、CTNNA2）的基因。
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