Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.
Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.
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DOI：
10.1002/dmrr.1031
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发表时间：
2009-11
影响因子：
8
通讯作者：
Hanson, Robert L.
中科院分区：
文献类型：
--
作者：
Malhotra, Alka;Igo, Robert P., Jr.;Thameem, Farook;Kao, W. H. Linda;Abboud, Hanna E.;Adler, Sharon G.;Arar, Nedal H.;Bowden, Donald W.;Duggirala, Ravindranath;Freedman, Barry I.;Goddard, Katrina A. B.;Ipp, Eli;Iyengar, Sudha K.;Kimmel, Paul L.;Knowler, William C.;Kohn, Orly;Leehey, David;Meoni, Lucy A.;Nelson, Robert G.;Nicholas, Susanne B.;Parekh, Rulan S.;Rich, Stephen S.;Chen, Yii-Der I.;Saad, Mohammed F.;Scavini, Marina;Schelling, Jeffrey R.;Sedor, John R.;Shah, Vallabh O.;Taylor, Kent D.;Thornley-Brown, Denyse;Zager, Philip G.;Horvath, Amanda;Hanson, Robert L.
先前的研究表明，除了环境影响外，2型糖尿病（T2 DM）具有很强的遗传成分。本研究的目的是确定不同种族人群中T2 DM的连锁区域。表型和基因型数据来自肾病和糖尿病家族调查的非裔美国人（AA;总个体数（N）=1004）、美洲印第安人（AI; N=883）、欧洲裔美国人（EA; N=537）和墨西哥裔美国人（MA; N=1634）个体。非参数连锁分析，使用平均4，404个SNP，在每个种族中受T2 DM影响的相对对中进行。此外，还进行了基于家族的检测，以检测与T2 DM的相关性。在AA的染色体4q21.1上观察到连锁的统计学显著证据（LOD=3.13;全基因组p=0.04）。此外，共有11个区域显示了连锁的暗示性证据（估计LOD>1.71），其中AA中染色体12q21.31（LOD=2.02）和22q12.3（LOD=2.38）、AI中染色体2p11.1（LOD=2.23）、EA中染色体6p12.3（LOD=2.77）和MA中染色体13q21.1（LOD=2.24）的LOD得分最高。虽然在所有种族群体中没有重叠的区域，但在先前发表的研究中已经确定了至少5个显示LOD>1.71的基因座。本研究的结果为AA中染色体4 q、12 q和22 q、EA中染色体6p、AI中染色体2 p和MA中染色体13 q上存在影响T2 DM的基因提供了证据。鉴于在该人群中缺乏糖尿病遗传学研究，AA中染色体4 q连锁的强有力证据提供了重要信息。
Previous studies have shown that, in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals (N)=1004), American Indian (AI; N=883), European American (EA; N=537), and Mexican American (MA; N=1634) individuals from the Family Investigation of Nephropathy and Diabetes. Nonparametric linkage analysis, using an average of 4,404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosomes 4q21.1 (LOD=3.13; genome-wide p=0.04) in AA. In addition, a total of eleven regions showed suggestive evidence for linkage (estimated at LOD>1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD=2.02) and 22q12.3 (LOD=2.38) in AA, 2p11.1 (LOD=2.23) in AI, 6p12.3 (LOD=2.77) in EA, and 13q21.1 (LOD=2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD>1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA, 6p in EA, 2p in AI, and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.
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