■尽管注意缺陷多动障碍(ADHD)被认为是一种多方面的神经发育障碍,其核心原因仍然模棱两可。这项研究的目的是探讨循环免疫细胞的特征是否对ADHD的易感性有因果关系。
■通过使用涵盖GWAS目录中731种免疫性状的统一GWAS汇总数据(登录号从GCST0001391到GCST0002121),我们的分析集中在淋巴细胞簇的流式细胞术,包括3,757名撒丁岛人,鉴定基因预期的免疫细胞。此外,我们从精神病学基因组学联盟获得了汇总的GWAS统计数据,以评估ADHD的遗传预测.这些研究采用了ADHD2019(来自2019年GWASADHD数据集的20,183例和35,191例对照)和ADHD2022(来自2022年GWASADHD数据集的38,691例和275,986例对照)。通过检查全基因组关联信号,我们确定了循环免疫细胞和多动症之间的共有遗传变异,采用全面的ADHD2022数据集。在孟德尔随机化研究和敏感性评估中,我们主要使用逆方差加权(IVW)和加权中位数方法来评估多样性和多效性。
■调整错误发现率(FDR)后,发现三种不同的免疫表型与ADHD风险相关:ImMDSC中的CD33(OR=1.03,CI:1.01〜1.04,P=3.04×10-5,PFDR=0.015),CD8brNKT%T细胞(OR=1.08,95CI:1.04~1.12,P=9.33×10-5,PFDR=0.023),和CD8brNKT%淋巴细胞(OR=1.08,95CI:1.03〜1.12,P=3.59×10-4,PFDR=0.066)。此外,ADHD对免疫表型无统计学影响。值得注意的是,存在20种表型,其中ADHD的出现可以减少85%的免疫细胞,髓样DC中包括FSC-A(β=-0.278,95%CI:0.616~0.931,P=0.008),CD45RA-CD4+中的CD3(β=-0.233,95%CI:0.654~0.960,P=0.017),CD62L-单核细胞AC(β=0.227,95%CI:0.038~1.518,P=0.019),CD33brHLADR+CD14dim中的CD33(β=-0.331,95%CI:0.543~0.950,P=0.020),CD39+静息Treg中的CD25(β=0.226,95%CI:1.522,P=0.022),单核细胞FSC-A(β=-0.255,95%CI:0.621~0.967,P=0.234),在其他人中。
■研究表明免疫系统的反应影响ADHD的出现。这些发现极大地改善了我们对免疫反应和多动症风险之间相互作用的理解。从免疫学的角度帮助发展治疗策略。
UNASSIGNED: Despite the recognition of attention deficit hyperactivity disorder (
ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this
study was to explore if the traits of circulating immune cells contribute causally to susceptibility to
ADHD.
UNASSIGNED: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS
ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy.
UNASSIGNED: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore,
ADHD showed no statistical effects on immunophenotypes. It\'s worth noting that 20 phenotypes exist where ADHD\'s appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (β= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (β= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (β=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (β= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (β=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (β= -0.255, 95% CI: 0.621~0.967, P=0.234), among others.
UNASSIGNED: Studies indicate that the immune system\'s response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.