Shinwari Jameela M A, Al Yemni Eman A A, Alnaemi Faten M, Abebe Dejene, Al-Abdulaziz Basma S, Al Mubarak Bashayer R, Ghaziuddin Mohammad, Al Tassan Nada A
aBehavioral Genetics Unit, Department of Genetics bDepartment of Psychiatry, King Faisal Specialist Hospital & Research Center cThe National Center for Genomic Technology, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia dDepartment of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
Psychiatr Genet. 2017 Aug;27(4):131-138. doi: 10.1097/YPG.0000000000000173.
Genetic and clinical complexities are common features of most psychiatric illnesses that pose a major obstacle in risk-gene identification. Attention deficit hyperactivity disorder (ADHD) is the most prevalent child-onset psychiatric illness, with high heritability. Over the past decade, numerous genetic studies utilizing various approaches, such as genome-wide association, candidate-gene association, and linkage analysis, have identified a multitude of candidate loci/genes. However, such studies have yielded diverse findings that are rarely reproduced, indicating that other genetic determinants have not been discovered yet. In this study, we carried out sib-pair analysis on seven multiplex families with ADHD from Saudi Arabia. We aimed to identify the candidate chromosomal regions and genes linked to the disease.
A total of 41 individuals from multiplex families were analyzed for shared regions of homozygosity. Genes within these regions were prioritized according to their potential relevance to ADHD.
We identified multiple genomic regions spanning different chromosomes to be shared among affected members of each family; these included chromosomes 3, 5, 6, 7, 8, 9, 10, 13, 17, and 18. We also found specific regions on chromosomes 8 and 17 to be shared between affected individuals from more than one family. Among the genes present in the regions reported here were involved in neurotransmission (GRM3, SIGMAR1, CHAT, and SLC18A3) and members of the HLA gene family (HLA-A, HLA-DPA1, and MICC).
The candidate regions identified in this study highlight the genetic diversity of ADHD. Upon further investigation, these loci may reveal candidate genes that enclose variants associated with ADHD. Although most ADHD studies were conducted in other populations, our study provides insight from an understudied, ethnically interesting population.
遗传和临床复杂性是大多数精神疾病的常见特征，这在风险基因识别中构成了主要障碍。注意力缺陷多动障碍（ADHD）是最常见的儿童期起病的精神疾病，具有高度遗传性。在过去十年中，众多利用各种方法（如全基因组关联、候选基因关联和连锁分析）的遗传研究已经鉴定出大量候选基因座/基因。然而，这些研究产生了多样且很少能重复的结果，这表明尚未发现其他遗传决定因素。在本研究中，我们对来自沙特阿拉伯的七个ADHD多重家庭进行了同胞对分析。我们旨在识别与该疾病相关的候选染色体区域和基因。
对来自多重家庭的41名个体进行了纯合性共享区域分析。根据这些区域内基因与ADHD的潜在相关性对其进行了优先级排序。
我们在每个家庭的患病成员中识别出跨越不同染色体的多个基因组区域；这些区域包括3号、5号、6号、7号、8号、9号、10号、13号、17号和18号染色体。我们还发现8号和17号染色体上的特定区域在不止一个家庭的患病个体之间共享。在此报告区域中存在的基因涉及神经传递（GRM3、SIGMAR1、CHAT和SLC18A3）以及HLA基因家族成员（HLA - A、HLA - DPA1和MICC）。
本研究中识别出的候选区域突出了ADHD的遗传多样性。经过进一步研究，这些基因座可能会揭示包含与ADHD相关变异的候选基因。尽管大多数ADHD研究是在其他人群中进行的，但我们的研究为一个研究较少且具有种族研究意义的人群提供了见解。
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