Chen J, Calhoun V D, Perrone-Bizzozero N I, Pearlson G D, Sui J, Du Y, Liu J
The Mind Research Network, Albuquerque, NM, USA.
Department of Electrical Engineering, University of New Mexico, Albuquerque, NM, USA.
Transl Psychiatry. 2016 May 31;6(5):e824. doi: 10.1038/tp.2016.96.
Schizophrenia (SZ) and bipolar disorder (BD) are known to share genetic risks. In this work, we conducted whole-genome scanning to identify cross-disorder and disorder-specific copy number variants (CNVs) for these two disorders. The Database of Genotypes and Phenotypes (dbGaP) data were used for discovery, deriving from 2416 SZ patients, 592 BD patients and 2393 controls of European Ancestry, as well as 998 SZ patients, 121 BD patients and 822 controls of African Ancestry. PennCNV and Birdsuite detected high-confidence CNVs that were aggregated into CNV regions (CNVRs) and compared with the database of genomic variants for confirmation. Then, large (size⩾500 kb) and small common CNVRs (size <500 kb, frequency⩾1%) were examined for their associations with SZ and BD. Particularly for the European Ancestry samples, the dbGaP findings were further evaluated in the Wellcome Trust Case Control Consortium (WTCCC) data set for replication. Previously implicated variants (1q21.1, 15q13.3, 16p11.2 and 22q11.21) were replicated. Some cross-disorder variants were noted to differentially affect SZ and BD, including CNVRs in chromosomal regions encoding immunoglobulins and T-cell receptors that were associated more with SZ, and the 10q11.21 small CNVR (GPRIN2) associated more with BD. Disorder-specific CNVRs were also found. The 22q11.21 CNVR (COMT) and small CNVRs in 11p15.4 (TRIM5) and 15q13.2 (ARHGAP11B and FAN1) appeared to be SZ-specific. CNVRs in 17q21.2, 9p21.3 and 9q21.13 might be BD-specific. Overall, our primary findings in individual disorders largely echo previous reports. In addition, the comparison between SZ and BD reveals both specific and common risk CNVs. Particularly for the latter, differential involvement is noted, motivating further comparative studies and quantitative models.
精神分裂症（SZ）和双相情感障碍（BD）已知存在共同的遗传风险。在本研究中，我们进行了全基因组扫描，以识别这两种疾病的跨疾病和疾病特异性拷贝数变异（CNV）。基因型和表型数据库（dbGaP）的数据用于发现，数据来源于2416名欧洲血统的SZ患者、592名BD患者和2393名对照，以及998名非洲血统的SZ患者、121名BD患者和822名对照。PennCNV和Birdsuite检测到高可信度的CNV，将其汇总为CNV区域（CNVR），并与基因组变异数据库进行比较以进行确认。然后，检查大的（大小⩾500 kb）和小的常见CNVR（大小<500 kb，频率⩾1%）与SZ和BD的关联。特别是对于欧洲血统的样本，在威康信托病例对照研究联盟（WTCCC）数据集中对dbGaP的发现进行了进一步评估以进行复制。先前涉及的变异（1q21.1、15q13.3、16p11.2和22q11.21）得到了复制。注意到一些跨疾病变异对SZ和BD有不同影响，包括编码免疫球蛋白和T细胞受体的染色体区域中的CNVR，其与SZ的关联更强，以及10q11.21小CNVR（GPRIN2）与BD的关联更强。还发现了疾病特异性的CNVR。22q11.21 CNVR（COMT）以及11p15.4（TRIM5）和15q13.2（ARHGAP11B和FAN1）中的小CNVR似乎是SZ特异性的。17q21.2、9p21.3和9q21.13中的CNVR可能是BD特异性的。总体而言，我们在个体疾病中的主要发现与先前的报告基本一致。此外，SZ和BD之间的比较揭示了特异性和共同的风险CNV。特别是对于后者，注意到了不同的参与情况，这激发了进一步的比较研究和定量模型。
