A Perception on Genome-Wide Genetic Analysis of Metabolic Traits in Arab Populations
A Perception on Genome-Wide Genetic Analysis of Metabolic Traits in Arab Populations
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DOI：
10.3389/fendo.2019.00008
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发表时间：
2019-01-28
影响因子：
5.2
通讯作者：
Thanaraj, Thangavel Alphonse
中科院分区：
文献类型：
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作者：
Hebbar, Prashantha;Abubaker, Jehad Ahmed;Thanaraj, Thangavel Alphonse
尽管在全国范围内致力于提高人们对快餐消费和久坐生活方式有害影响的认识，但阿拉伯人口仍在与代谢紊乱风险增加作斗争。与欧洲人群不同，阿拉伯人群缺乏代谢紊乱的明确遗传风险决定因素，并且已确定的风险位点向该人群的可转移性尚未得到令人满意的证明。最近的研究结果已确定了 2 型糖尿病的 240 多个遗传风险位点（类似于 400 个独立关联信号），但迄今为止只有 25 个风险位点（ADAMTS9、ALX4、BCL11A、CDKAL1、CDKN2A/B、COL8A1、DUSP9、FTO、GCK、GNPDA2、HMG20A、HNF1A、HNF1B、 HNF4A、IGF2BP2、JAZF1、KCNJ11、KCNQ1、MC4R、PPAR gamma、SLC30A8、TCF7L2、TFAP2B、TP53INP1 和 WFS1）已在阿拉伯人群中复制。据我们所知，该地区不存在大规模的人口或家庭关联研究。最近，我们对科威特的阿拉伯人进行了全基因组关联研究，以描绘与人体测量、血脂、胰岛素抵抗和血压水平相关的数量性状的遗传决定因素。尽管这些研究导致了新的隐性变异的鉴定，但它们未能重现已建立的基因座。然而，他们提供了对人口遗传结构、基于隐性遗传模式的遗传模型的适用性、由于近亲结婚而存在的近亲繁殖遗传特征以及罕见疾病对复杂代谢紊乱的多效性影响的见解。该观点提出了用于识别阿拉伯人群中与糖尿病和相关特征相关的遗传风险变异的分析策略和研究设计。
Despite dedicated nation-wide efforts to raise awareness against the harmful effects of fast-food consumption and sedentary lifestyle, the Arab population continues to struggle with an increased risk for metabolic disorders. Unlike the European population, the Arab population lacks well-established genetic risk determinants for metabolic disorders, and the transferability of established risk loci to this population has not been satisfactorily demonstrated. The most recent findings have identified over 240 genetic risk loci (with similar to 400 independent association signals) for type 2 diabetes, but thus far only 25 risk loci (ADAMTS9, ALX4, BCL11A, CDKAL1, CDKN2A/B, COL8A1, DUSP9, FTO, GCK, GNPDA2, HMG20A, HNF1A, HNF1B, HNF4A, IGF2BP2, JAZF1, KCNJ11 , KCNQ1, MC4R, PPAR gamma, SLC30A8, TCF7L2, TFAP2B, TP53INP1, and WFS1) have been replicated in Arab populations. To our knowledge, large-scale population- or family-based association studies are non-existent in this region. Recently, we conducted genome-wide association studies on Arab individuals from Kuwait to delineate the genetic determinants for quantitative traits associated with anthropometry, lipid profile, insulin resistance, and blood pressure levels. Although these studies led to the identification of novel recessive variants, they failed to reproduce the established loci. However, they provided insights into the genetic architecture of the population, the applicability of genetic models based on recessive mode of inheritance, the presence of genetic signatures of inbreeding due to the practice of consanguinity, and the pleiotropic effects of rare disorders on complex metabolic disorders. This perspective presents analysis strategies and study designs for identifying genetic risk variants associated with diabetes and related traits in Arab populations.