Yang Yuanhao, Zhou Yuan, Nyholt Dale R, Yap Chloe X, Tannenberg Rudolph K, Wang Ying, Wu Yang, Zhu Zhihong, Taylor Bruce V, Gratten Jacob
Mater Research Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
Cell Genom. 2023 Jan 25;3(2):100249. doi: 10.1016/j.xgen.2022.100249. eCollection 2023 Feb 8.
Phenotypic associations have been reported between blood cell traits (BCTs) and a range of neurological and psychiatric disorders (NPDs), but in most cases, it remains unclear whether these associations have a genetic basis and, if so, to what extent genetic correlations reflect causality. Here, we report genetic correlations and Mendelian randomization analyses between 11 NPDs and 29 BCTs, using genome-wide association study summary statistics. We found significant genetic correlations for four BCT-NPD pairs, all of which have prior evidence for a phenotypic correlation. We identified a previously unreported causal effect of increased platelet distribution width on susceptibility to Parkinson's disease. We identified multiple functional genes and regulatory elements for specific BCT-NPD pairs, some of which are targets of known drugs. These results enrich our understanding of the shared genetic landscape underlying BCTs and NPDs and provide a robust foundation for future work to improve prognosis and treatment of common NPDs.
血细胞性状（BCTs）与一系列神经和精神疾病（NPDs）之间已报道有表型关联，但在大多数情况下，尚不清楚这些关联是否具有遗传基础，如果有，遗传相关性在多大程度上反映因果关系。在此，我们利用全基因组关联研究汇总统计数据，报告了11种NPDs与29种BCTs之间的遗传相关性和孟德尔随机化分析。我们发现了四对BCT-NPD具有显著的遗传相关性，所有这些在之前都有表型相关性的证据。我们确定了血小板分布宽度增加对帕金森病易感性的一种先前未报道的因果效应。我们为特定的BCT-NPD对鉴定了多个功能基因和调控元件，其中一些是已知药物的靶点。这些结果丰富了我们对BCTs和NPDs共同遗传背景的理解，并为未来改善常见NPDs的预后和治疗的工作提供了坚实基础。
