Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population
Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population
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DOI：
10.1016/j.gene.2018.08.041
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发表时间：
2018-11-30
期刊：
影响因子：
3.5
通讯作者：
Diaz-Badillo, Alvaro
中科院分区：
文献类型：
--
作者：
Givisay Dominguez-Cruz, Miriam;de Lourdes Munoz, Maria;Diaz-Badillo, Alvaro
2型糖尿病（T2 D）是墨西哥死亡的两大主要原因之一。然而，大多数研究都集中在高加索人或亚洲人身上，也有少数研究调查了玛雅人。此外，据我们所知，没有关于主要归因于种族的T2 D频率为20%的孤立玛雅社区的信息。因此，这项研究的重点是评估哪些遗传风险变异可能与92名玛雅血统个体的T2 D高发病率有关; 47名被诊断患有T2 D，45名被归类为健康个体。使用Affytron Axiom全基因组LAT 1阵列进行了一项试点全基因组关联研究。使用ADMIXTURE软件使用1289个拉丁美洲选择的多态性来确定群体结构，并且包括与T2 D相关的39个多态性用于复制。使用统计分析系统（SAS），使用等位基因，基因型和阿米蒂奇趋势检验进行关联检验。结果表明，群体结构分析显示T2 D患者和健康个体之间没有差异;定位的24个位点与T2 D可能相关（p > 1.288 x 10（-7）和p < 1.348 x 10（-4））;等位基因检测证实AGTR 2 rs 1914711在X染色体上存在多态性（OR = 6.824; p = 1.448 x 10（-9））作为与T2 D相关的候选基因; ARL 15 rs 4311394通过基因型和Armitage趋势检验（OR = 0.318; p = 0.001）作为T2 D保护基因相关。总之，本研究提出了24个与T2 D相关的候选SNP用于复制研究，并提出了一个与T2 D保护性相关的候选SNP。
Type 2 diabetes mellitus (T2D) is one of the two leading causes of mortality in Mexico. However, most studies have focused on Caucasians or Asians, and there are a small number of studies investigating Maya populations. Furthermore, to the best of our knowledge, there is no information on isolated Maya communities with T2D frequencies of 20% that are primarily attributed to ethnicity. Consequently, this study focused on assessing which genetic risk variants could be involved in the high rates of T2D in 92 individuals with Maya ancestry; 47 were diagnosed with T2D, and 45 were classified as healthy individuals. A pilot genome-wide association study was performed using the Affymetrix Axiom Genome-wide LAT1 array. The population structure was determined with the ADMIXTURE software using 1289 Latin American selected polymorphisms, and 39 polymorphisms associated with T2D were included for replication. Association tests were performed using the Statistical Analysis System (SAS) using the allelic, genotype and Armitage trend tests. The results indicated that population structure analysis displayed no differences between T2D patients and healthy individuals; 24 loci located were identified for probable association with T2D (p > 1.288 x 10(-7) and p < 1.348 x 10(-4)); the polymorphism AGTR2 rs1914711 in chromosome X was identified by the allele test (OR = 6.824; p = 1.448 x 10(-9)) as a candidate gene for association with T2D; and ARL15 rs4311394 was associated as a T2D protector by genotype and the Armitage trend test (OR = 0.318; p = 0.001). In conclusion, this study proposes 24 candidate SNPs associated with T2D for replication studies and one for protective association with T2D.