NUS1 has been recently identified as a candidate gene for Parkinson's disease (PD). Few studies have examined the association of NUS1 variants with PD susceptibility and phenotypes. In the first cohort, whole-exome sequencing was performed to identify variants in NUS1 exon-coding and exon-intron regions in 1542 cases and 1625 controls. 13 variants were totally detected, of which 10 rare variants and 3 low-frequency variants. Burden analysis showed that rare NUS1 variants significantly enriched in PD (P=0.016). We also performed a meta-analysis based on previous and our studies to correlate NUS1 mutations with PD susceptibility. Integrating our previous cohort (3210 cases and 2807 controls) and the first cohort identified the significant association of rs539668656 with PD risk (odds ratio(OR) = 2.82, P = 0.016). The genotype-phenotype association analysis showed that patients carrying rare variants, or rs539668656 were significantly associated with earlier onset age, depression, emotional impairment and severe disease condition. Our results support the role of NUS1 rare variants and rs539668656 towards PD susceptibility and phenotype.

NUS1最近已被确定为帕金森病 (PD) 的候选基因。很少有研究检查NUS1变体与 PD 易感性和表型的关联。在第一个队列中，进行了全外显子组测序以鉴定1542 例病例和 1625 例对照中NUS1外显子编码和外显子-内含子区域的变异。共检测到13个变异，其中罕见变异10个，低频变异3个。负担分析表明，罕见的NUS1变体在 PD 中显着富集（ P = 0.016）。我们还根据之前和我们的研究进行了荟萃分析，以关联NUS1具有 PD 易感性的突变。整合我们之前的队列（3210 例病例和 2807 例对照）和第一个队列确定了 rs539668656 与 PD 风险的显着关联（优势比 (OR) = 2.82，P = 0.016）。基因型-表型关联分析表明，携带罕见变异或 rs539668656 的患者与早发年龄、抑郁、情绪障碍和严重疾病状况显着相关。我们的结果支持NUS1罕见变异和 rs539668656 对 PD 易感性和表型的作用。