背景:已知ADHD先证者的亲属患精神分裂症和双相情感障碍的风险增加,提示共同的遗传因素。在这项研究中,我们的目标是识别共同的风险变体(即,单核苷酸多态性,SNP)在ADHD和精神分裂症之间,多动症和双相情感障碍之间。
方法:使用来自三个GWAS的汇总数据,1例ADHD(20,183例ADHD和35,191例对照),另一个关于精神分裂症(76,755例精神分裂症和243,649例对照),另一个关于双相情感障碍(41,917例双相情感障碍和371,549例对照),我们使用共定位分析来识别ADHD和精神分裂症共有的SNP,和多动症和双相情感障碍共有的SNP。然后对这两组共有的共同遗传变体进行功能基因组分析。
结果:我们发现与ADHD相关的12个SNPs中有3个与精神分裂症SNPs共同定位,与ADHD相关的12个SNPs中有1个与双相情感障碍共同定位。与精神分裂症相关的SNP只有0.4%(431个中的2个)和与双相情感障碍相关的SNP的2.3%(86个中的2个),与ADHDSNP共同定位。一些映射到这些共有遗传变异体(SCN2A和UNC5D)的基因参与神经系统的发育。
结论:使用共定位分析,本研究揭示了与ADHD和精神分裂症以及ADHD和双相情感障碍相关的共有遗传变异,并且可能至少部分解释了多动症先证者亲属患精神分裂症和双相情感障碍的风险增加。
BACKGROUND: Relatives of ADHD probands are known to be at increased risk of schizophrenia and bipolar disorder, suggesting shared genetic factors. In this study, we aim to identify shared common risk variants (i.e., Single-Nucleotide Polymorphisms, SNPs) between ADHD and schizophrenia, and between ADHD and bipolar disorder.
METHODS: With the summary data from three GWAS, one on ADHD (20,183 cases with ADHD and 35,191 controls), another on schizophrenia (76,755 cases with schizophrenia and 243,649 controls) and another on bipolar disorder (41,917 cases with bipolar disorder and 371,549 controls), we used colocalization analysis to identify SNPs shared by ADHD and schizophrenia, and SNPs shared by ADHD and bipolar disorder. Functional genomic analyses were then conducted on these two sets of shared common genetic variants.
RESULTS: We found that three of the 12 SNPs associated with ADHD colocalized with schizophrenia SNPs and one of the 12 SNPs associated with ADHD colocalized with bipolar disorder. Only 0.4% of the SNPs associated with schizophrenia (2 out of 431) and 2.3% of the SNPs associated with bipolar disorder (2 out of 86), colocalized with ADHD SNPs. Some genes mapped to these shared genetic variants (SCN2A and UNC5D) are involved in the development of the nervous system.
CONCLUSIONS: Using colocalization analysis, the present study uncovers shared genetic variants associated with ADHD and schizophrenia as well as ADHD and bipolar disorder, and may at least partially explain the increased risk of schizophrenia and bipolar disorder in relatives of ADHD probands.