Hayes M Geoffrey, Pluzhnikov Anna, Miyake Kazuaki, Sun Ying, Ng Maggie C Y, Roe Cheryl A, Below Jennifer E, Nicolae Raluca I, Konkashbaev Anuar, Bell Graeme I, Cox Nancy J, Hanis Craig L
Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC6091, Chicago, IL 60637, USA.
Diabetes. 2007 Dec;56(12):3033-44. doi: 10.2337/db07-0482. Epub 2007 Sep 10.
The objective of this study was to identify DNA polymorphisms associated with type 2 diabetes in a Mexican-American population.
We genotyped 116,204 single nucleotide polymorphisms (SNPs) in 281 Mexican Americans with type 2 diabetes and 280 random Mexican Americans from Starr County, Texas, using the Affymetrix GeneChip Human Mapping 100K set. Allelic association exact tests were calculated. Our most significant SNPs were compared with results from other type 2 diabetes genome-wide association studies (GWASs). Proportions of African, European, and Asian ancestry were estimated from the HapMap samples using structure for each individual to rule out spurious association due to population substructure.
We observed more significant allelic associations than expected genome wide, as empirically assessed by permutation (14 below a P of 1 x 10(-4) [8.7 expected]). No significant differences were observed between the proportion of ancestry estimates in the case and random control sets, suggesting that the association results were not likely confounded by substructure. A query of our top approximately 1% of SNPs (P < 0.01) revealed SNPs in or near four genes that showed evidence for association (P < 0.05) in multiple other GWAS interrogated: rs979752 and rs10500641 near UBQLNL and OR52H1 on chromosome 11, rs2773080 and rs3922812 in or near RALGPS2 on chromosome 1, and rs1509957 near EGR2 on chromosome 10.
We identified several SNPs with suggestive evidence for replicated association with type 2 diabetes that merit further investigation.
本研究的目的是在墨西哥裔美国人中鉴定与2型糖尿病相关的DNA多态性。
我们使用Affymetrix GeneChip Human Mapping 100K芯片组，对281名患有2型糖尿病的墨西哥裔美国人和280名来自得克萨斯州斯塔尔县的随机墨西哥裔美国人的116,204个单核苷酸多态性（SNP）进行基因分型。计算等位基因关联精确检验。将我们最显著的SNP与其他2型糖尿病全基因组关联研究（GWAS）的结果进行比较。使用structure软件从HapMap样本中估计每个个体的非洲、欧洲和亚洲血统比例，以排除由于人群亚结构导致的虚假关联。
经置换法经验评估，我们观察到的显著等位基因关联比全基因组预期的更多（14个P值低于1×10⁻⁴[预期为8.7个]）。病例组和随机对照组的血统估计比例之间未观察到显著差异，这表明关联结果不太可能因亚结构而混淆。对我们约前1%的SNP（P<0.01）进行查询发现，在其他多个GWAS中显示有关联证据（P<0.05）的四个基因内或附近存在SNP：11号染色体上UBQLNL和OR52H1附近的rs979752和rs10500641，1号染色体上RALGPS2内或附近的rs277,3080和rs3922812，以及10号染色体上EGR2附近的rs1509957。
我们鉴定出了几个SNP，有提示性证据表明其与2型糖尿病存在重复关联，值得进一步研究。
