While the Arabian population has a high prevalence of metabolic disorders, it has not been included in global studies that identify genetic risk loci for metabolic traits. Determining the transferability of such largely Euro-centric established risk loci is essential to transfer the research tools/resources, and drug targets generated by global studies to a broad range of ethnic populations. Further, consideration of populations such as Arabs, that are characterized by consanguinity and a high level of inbreeding, can lead to identification of novel risk loci. We imputed published GWAS data from two Kuwaiti Arab cohorts (n = 1434 and 1298) to the 1000 Genomes Project haplotypes and performed meta-analysis for associations with 13 metabolic traits. We compared the observed association signals with those established for metabolic traits. Our study highlighted 70 variants from 9 different genes, some of which have established links to metabolic disorders. By relaxing the genome-wide significance threshold, we identified ‘novel’ risk variants from 11 genes for metabolic traits. Many novel risk variant association signals were observed at or borderline to genome-wide significance. Furthermore, 349 previously established variants from 187 genes were validated in our study. Pleiotropic effect of risk variants on multiple metabolic traits were observed. Fine-mapping illuminated rs7838666/CSMD1 rs1864163/CETP and rs112861901/[INTS10,LPL] as candidate causal variants influencing fasting plasma glucose and high-density lipoprotein levels. Computational functional analysis identified a variety of gene regulatory signals around several variants. This study enlarges the population ancestry diversity of available GWAS and elucidates new variants in an ethnic group burdened with metabolic disorders.

尽管阿拉伯人口的代谢紊乱患病率很高，但尚未将其纳入识别代谢性状遗传风险基因座的全球研究中。确定这样大量以欧洲为中心的已建立风险基因座的可转移性，对于将研究工具/资源以及全球研究产生的毒品目标转移给广泛的种族人群至关重要。此外，考虑到具有阿拉伯血统和高度近亲繁殖特征的阿拉伯人等人口，可以导致确定新的风险基因座。我们估算了来自两个科威特阿拉伯队列（n = 1434和1298）到1000个基因组计划单倍型，并进行了与13种代谢性状相关的荟萃分析。我们将观察到的关联信号与为代谢性状建立的关联信号进行了比较。我们的研究突出了来自9个不同基因的70个变体，其中一些已与代谢紊乱建立了联系。通过放宽全基因组重要性阈值，我们从代谢性状的11个基因中鉴定了“新”风险变异。在全基因组意义上或在其意义上观察到许多新的风险变异关联信号。此外，在我们的研究中验证了来自187个基因的349个先前建立的变体。观察到风险变异对多种代谢性状的多效性。精细映射的rs7838666 / CSMD1 rs1864163 / CETP和rs112861901 / [ INTS10，LPL ]作为影响空腹血糖和高密度脂蛋白水平的候选因果变体。计算功能分析确定了围绕几种变体的多种基因调控信号。这项研究扩大了可用的GWAS的族谱多样性，并阐明了患有代谢异常的族裔中的新变异。