Division of Psychiatry, the University of Western Australia, Crawley, Western Australia, Australia.
School of Human Science, The University of Western Australia, Crawley, Western Australia, Australia.
BMC Psychiatry. 2020 Jan 31;20(1):41. doi: 10.1186/s12888-019-2425-8.
Genome Wide Association Studies (GWAS) have been conducted to identify genes and pathways involved in development of opioid use disorder. This study extends the first GWAS of substance use disorder (SUD) patients from the United Arab Emirates (UAE) by stratifying the study group based on opioid use, which is the most common substance of use in this cohort.
The GWAS cohort consisted of 512 (262 case, 250 controls) male participants from the UAE. The samples were genotyped using the Illumina Omni5 Exome system. Data was stratified according to opioid use using PLINK. Haplotype analysis was conducted using Haploview 4.2.
Two main associations were identified in this study. Firstly, two SNPs on chromosome 7 were associated with opioid use disorder, rs118129027 (p-value = 1.23 × 10 ) and rs74477937 (p-value = 1.48 × 10 ). This has been reported in Alblooshi et al. (Am J Med Genet B Neuropsychiatr Genet 180(1):68-79, 2019). Secondly, haplotypes on chromosome 2 which mapped to the KIAA1211L locus were identified in association with opioid use. Five SNPs in high linkage disequilibrium (LD) (rs2280142, rs6542837, rs12712037, rs10175560, rs11900524) were arranged into haplotypes. Two haplotypes GAGCG and AGTTA were associated with opioid use disorders (p-value 3.26 × 10 and 7.16 × 10, respectively).
This is the first GWAS to identify candidate genes associated with opioid use disorder in participants from the UAE. The lack of other genetic data of Arabian descent opioid use patients has hindered replication of the findings. Nevertheless, the outcomes implicate new pathways in opioid use disorder that requires further research to assess the role of the identified genes in the development of opioid use disorder.
全基因组关联研究（GWAS）已被用于鉴定与阿片类药物使用障碍相关的基因和通路。本研究通过对阿联酋（UAE）的研究人群进行基于阿片类药物使用的分层，扩展了首个阿片类物质使用障碍（SUD）患者的 GWAS。
GWAS 队列由 512 名（262 例病例，250 例对照）男性阿联酋参与者组成。样本使用 Illumina Omni5 Exome 系统进行基因分型。使用 PLINK 根据阿片类药物使用对数据进行分层。使用 Haploview 4.2 进行单倍型分析。
本研究确定了两个主要关联。首先，在第 7 号染色体上的两个 SNP，rs118129027（p 值=1.23×10）和 rs74477937（p 值=1.48×10），与阿片类药物使用障碍相关，这在 Alblooshi 等人的研究中已有报道（Am J Med Genet B Neuropsychiatr Genet 180(1):68-79, 2019）。其次，在与阿片类药物使用相关的染色体 2 上，鉴定到与 KIAA1211L 基因座映射的单倍型。五个处于高度连锁不平衡（LD）的 SNPs（rs2280142、rs6542837、rs12712037、rs10175560、rs11900524）被排列成单倍型。两个单倍型 GAGCG 和 AGTTA 与阿片类药物使用障碍相关（p 值分别为 3.26×10 和 7.16×10）。
这是在阿联酋参与者中鉴定与阿片类药物使用障碍相关候选基因的首个 GWAS。缺乏其他具有阿拉伯血统的阿片类药物使用患者的遗传数据，阻碍了研究结果的复制。尽管如此，这些结果提示了阿片类药物使用障碍的新途径，需要进一步研究来评估所鉴定基因在阿片类药物使用障碍发展中的作用。
