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） 的常见早期症状。嗅觉减退和 PD 之间的共同遗传结构尚不清楚。我们利用全基因组关联研究 （GWAS） 结果对“嗅觉能力”和 PD 诊断进行自我评估，以确定两个性状之间的共同遗传结构。连锁不平衡评分 （LDSC） 回归发现，嗅觉在全基因组水平上与 PD 呈负相关。[co]Variant Association （LAVA） 的局部分析发现 GBA1、ANAPC4、SNCA 和 MAPT 附近的四个遗传位点呈负相关，表明仅在突出的 PD 风险基因子集内存在共同的遗传倾向。使用孟德尔随机化，我们发现有证据表明 PD 与嗅觉较差的易感倾向之间存在很强的因果关系，但相反方向的证据较弱。这项工作强调了嗅觉功能的遗传性及其与 PD 遗传性的关系，并进一步揭示了 PD 与嗅觉减退之间的关联。