Kim Jonggeol Jeffrey, Bandres-Ciga Sara, Heilbron Karl, Blauwendraat Cornelis, Noyce Alastair J
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
NPJ Parkinsons Dis. 2024 Dec 5;10(1):232. doi: 10.1038/s41531-024-00838-4.
Hyposmia (decreased smell function) is a common early symptom of Parkinson's disease (PD). The shared genetic architecture between hyposmia and PD is unknown. We leveraged genome-wide association study (GWAS) results for self-assessment of 'ability to smell' and PD diagnosis to determine shared genetic architecture between the two traits. Linkage disequilibrium score (LDSC) regression found that the sense of smell negatively correlated at a genome-wide level with PD. Local Analysis of [co]Variant Association (LAVA) found negative correlations in four genetic loci near GBA1, ANAPC4, SNCA, and MAPT, indicating shared genetic liability only within a subset of prominent PD risk genes. Using Mendelian randomization, we found evidence for a strong causal relationship between PD and liability towards poorer sense of smell, but weaker evidence for the reverse direction. This work highlights the heritability of olfactory function and its relationship with PD heritability and provides further insight into the association between PD and hyposmia.
嗅觉减退（嗅觉功能下降）是帕金森病（PD）常见的早期症状。嗅觉减退与帕金森病之间共享的遗传结构尚不清楚。我们利用全基因组关联研究（GWAS）中关于“嗅觉能力”自我评估和帕金森病诊断的结果，来确定这两个性状之间共享的遗传结构。连锁不平衡评分（LDSC）回归发现，在全基因组水平上，嗅觉与帕金森病呈负相关。[共]变体关联局部分析（LAVA）发现在GBA1、ANAPC4、SNCA和MAPT附近的四个基因位点存在负相关，表明仅在一部分主要的帕金森病风险基因中存在共享的遗传易感性。使用孟德尔随机化方法，我们发现有证据表明帕金森病与嗅觉较差的易感性之间存在很强的因果关系，但反向关系的证据较弱。这项工作突出了嗅觉功能的遗传性及其与帕金森病遗传性的关系，并为帕金森病与嗅觉减退之间的关联提供了进一步的见解。
