Farook Vidya S, Coletta Dawn K, Puppala Sobha, Schneider Jennifer, Chittoor Geetha, Hu Shirley L, Winnier Deidre A, Norton Luke, Dyer Thomas D, Arya Rector, Cole Shelley A, Carless Melanie, Göring Harald H, Almasy Laura, Mahaney Michael C, Comuzzie Anthony G, Curran Joanne E, Blangero John, Duggirala Ravindranath, Lehman Donna M, Jenkinson Christopher P, Defronzo Ralph A
Southwest Foundation for Biomedical Research, San Antonio, Tex., USA.
Hum Hered. 2013;76(1):36-46. doi: 10.1159/000354849. Epub 2013 Sep 21.
Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans.
We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence.
After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10(-6)). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10(-5), genome-wide p = 1.6 × 10(-3)) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data.
Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.
2型糖尿病（T2DM）是一种复杂的代谢性疾病，在某些种族群体如墨西哥裔美国人中更为普遍。我们研究的目的是进行全基因组连锁（GWL）分析，以定位墨西哥裔美国人中T2DM的易感基因座。
我们使用了来自参与退伍军人管理局遗传流行病学研究（VAGES）的1122名墨西哥裔美国人（307个家庭）的表型和基因型数据。使用方差成分法进行GWL分析。来自另外两项墨西哥裔美国家庭研究，即圣安东尼奥家庭心脏研究（SAFHS）和圣安东尼奥家庭糖尿病/胆囊研究（SAFDGS）的数据与VAGES数据相结合，以检验是否有更强有力的连锁证据。
在调整协变量效应后，发现T2DM受到显著的遗传影响（h2 = 0.62，p = 2.7×10⁻⁶）。T2DM连锁的最强证据出现在9号染色体p24.2 - p24.1上的标记D9S1871和D9S2169之间（LOD = 1.8）。鉴于我们之前在SAFDGS中也报告了该区域T2DM连锁的提示性证据，当我们对VAGES数据与SAFHS和SAFDGS数据进行GWL分析时，我们在同一染色体区域发现了T2DM的显著且增强的连锁证据（LOD = 4.3，经验性p = 1.0×10⁻⁵，全基因组p = 1.6×10⁻³）。
在墨西哥裔美国人的9号染色体p24上发现了显著的T2DM连锁证据。重要的是，本研究中感兴趣的染色体区域与最近几项涉及T2DM相关性状的全基因组关联研究重叠。鉴于其与这些发现以及我们自己在9号染色体p24区域的初始T2DM关联发现重叠，对连锁染色体区域进行高通量测序可能会鉴定出潜在的导致T2DM的基因。
