School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Crawley, Western Australia, Australia.
School of Human Science, The University of Western Australia, Crawley, Western Australia, Australia.
Am J Med Genet B Neuropsychiatr Genet. 2019 Jan;180(1):68-79. doi: 10.1002/ajmg.b.32708. Epub 2018 Dec 16.
Genome wide association studies (GWASs) have provided insights into the molecular basis of the disorder in different population. This study presents the first GWAS of substance use disorder (SUD) in patients from the United Arab Emirates (UAE). The aim was to identify genetic association(s) that may provide insights into the molecular basis of the disorder. The GWAS discovery cohort consisted of 512 (250 cases and 262 controls) male participants from the UAE. Controls with no prior history of SUD were available from the Emirates family registry. The replication cohort consisted of 520 (415 cases and 105 controls) Australian male Caucasian participants. The GWAS discovery samples were genotyped for 4.6 million single nucleotide polymorphism (SNP). The replication cohort was genotyped using TaqMan assay. The GWAS association analysis identified three potential SNPs rs118129027 (p-value = 6.24 × 10 ), rs74477937 (p-value = 8.56 × 10 ) and rs78707086 (p-value = 8.55 × 10 ) on ch7p14.1, that did not meet the GWAS significance threshold but were highly suggestive. In the replication cohort, the association of the three top SNPs did not reach statistical significance. In a meta-analysis of the discovery and the replication cohorts, there were no strengthen evidence for association of the three SNPs. The top identified rs118129027 overlaps with a regulatory factor (enhancer) region that targets three neighboring genes LOC105375237, LOC105375240, and YAE1D1. The YAE1D1, which represents a potential locus that is involved in regulating translation initiation pathway. Novel associations that require further confirmation were identified, suggesting a new insight to the genetic basis of SUD.
全基因组关联研究（GWAS）为不同人群中该疾病的分子基础提供了新的见解。本研究报告了阿拉伯联合酋长国（UAE）患者物质使用障碍（SUD）的首次 GWAS。目的是确定可能为该疾病的分子基础提供新见解的遗传关联。GWAS 发现队列由来自阿联酋的 512 名男性参与者（250 例病例和 262 名对照）组成。阿联酋家族登记处提供了无先前 SUD 病史的对照者。复制队列由 520 名澳大利亚男性白种人参与者（415 例病例和 105 名对照）组成。GWAS 发现样本对 460 万个单核苷酸多态性（SNP）进行了基因分型。使用 TaqMan 测定法对复制队列进行基因分型。GWAS 关联分析确定了三个潜在的 SNP rs118129027（p 值=6.24×10），rs74477937（p 值=8.56×10）和 rs78707086（p 值=8.55×10）位于 7p14.1 上，未达到 GWAS 显著性阈值，但高度提示。在复制队列中，三个顶级 SNP 的关联未达到统计学意义。在发现队列和复制队列的荟萃分析中，三个 SNP 的关联没有加强证据。鉴定出的 top SNP rs118129027 与靶向三个邻近基因 LOC105375237、LOC105375240 和 YAE1D1 的调节因子（增强子）区域重叠。YAE1D1 代表一个潜在的基因座，涉及调节翻译起始途径。需要进一步确认的新关联已被确定，这为 SUD 的遗传基础提供了新的见解。
