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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：
我们先前通过对GENNID样本的非洲裔美国人中的T2D和诊断年龄（AOD）的全基因组连锁扫描，将2型糖尿病（T2D）易感基因定位到五个染色体区域。为了跟进这些发现，我们使用基因型对另外9203个精细作图的单核苷酸多态性(SNPs)重复了连锁和关联分析,这些单核苷酸多态性被选择用于标记连锁峰下的基因.在这五个地区中，我们确认了连锁并推断存在≥2个易感基因.多个易感基因的证据包括：（1）五个区域中四个区域的多个连锁峰；（2）T2D和AOD与每个区域中≥2个基因内的SNP的关联。相关基因包括3个先前报道的与T2D或相关性状相关的基因(GRB10，NEDD4L，LIPG）和24个新的候选基因，包括脂质代谢中的基因（ACOXL）和细胞-细胞和细胞-基质粘附（MAGI2，CLDN4，CTNNA2）。
