The Mind Research Network, Albuquerque, NM, USA; Dept. of Electrical Engineering, University of New Mexico, Albuquerque, NM, USA.
The Mind Research Network, Albuquerque, NM, USA.
Schizophr Res. 2018 Feb;192:240-246. doi: 10.1016/j.schres.2017.04.033. Epub 2017 Apr 22.
Both schizophrenia (SZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. The significant genomic risk loci are of great importance but with no guarantee of known functional impact and they cannot totally explain the genetic inheritance. In this study we present regional enrichment analyses across the genome, aiming to strike a balance between individual risk loci and integrated regional effects. Chromosomes were partitioned into 2 million base-pair regions (indicated by an underscore sign in the cytogenetic bands) on which enrichment tests are performed. In the discovery phase, we leverage the Psychiatric Genomics Consortium SZ and BD initial association test results for European Ancestry (EA) population and dbGAP SNP data for African Ancestry (AA) population. 78 and 48 regions show significantly enriched associations with SZ and BD respectively in the EA population, and nine are in common including MHC, 3p21.1, 7p22.3_2, 2q32.3_2, 8q24.3_4, and 19q13.33_1. The most unique SZ associated region is 1p21.3_3, while the most unique BD associated region is 6q25.2_1. For the AA population fewer regions are discovered with only 10% overlapping with that of EA population. A replication test using Wellcome Trust Case Control Consortium data for EA population verified 9% of the SZ enriched regions and 40% of the BD enriched regions. In summary, we showed that regional enrichment analyses produce reliable genetic association profiles using about one tenth of samples compared to single base-pair genome wide association approach. The identified association regions will be useful for further genetic functional studies.
精神分裂症（SZ）和双相情感障碍（BD）都是高度遗传性的精神疾病。重要的基因组风险基因座具有重要意义，但不能保证具有已知的功能影响，并且它们不能完全解释遗传继承。在这项研究中，我们在整个基因组中进行了区域富集分析，旨在在个体风险基因座和综合区域效应之间取得平衡。染色体被分成 200 万个碱基对区域（在细胞遗传带中用下划线表示），在这些区域上进行富集测试。在发现阶段，我们利用精神疾病基因组学联盟 SZ 和 BD 对欧洲血统（EA）人群的初始关联测试结果以及非洲血统（AA）人群的 dbGAP SNP 数据进行了研究。在 EA 人群中，有 78 个和 48 个区域分别与 SZ 和 BD 显著富集相关，其中 9 个区域是共同的，包括 MHC、3p21.1、7p22.3_2、2q32.3_2、8q24.3_4 和 19q13.33_1。与 SZ 最相关的独特区域是 1p21.3_3，而与 BD 最相关的独特区域是 6q25.2_1。对于 AA 人群，发现的区域较少，只有 10%与 EA 人群重叠。使用 EA 人群的惠康信托基金病例对照联盟数据进行的复制测试验证了 9%的 SZ 富集区域和 40%的 BD 富集区域。总之，与全基因组单碱基对关联方法相比，我们使用约十分之一的样本进行区域富集分析，产生了可靠的遗传关联图谱。鉴定出的关联区域将有助于进一步的遗传功能研究。
