Overlapping genetic architecture between Parkinson disease and melanoma
Overlapping genetic architecture between Parkinson disease and melanoma
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DOI：
10.1007/s00401-019-02110-z
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发表时间：
2020-02-01
影响因子：
12.7
通讯作者：
Cruchaga, Carlos
中科院分区：
文献类型：
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作者：
Dube, Umber;Ibanez, Laura;Cruchaga, Carlos
流行病学研究报告了关于帕金森病（PD）和皮肤黑色素瘤（黑色素瘤）之间关联的不一致结果。确定这些疾病之间共享的遗传结构可以支持流行病学研究结果，并确定共同的风险基因和生物学途径。在这里，我们应用多基因，连锁不平衡的方法，以最大的可用病例对照，全基因组关联研究黑色素瘤和PD的汇总统计数据。我们确定了黑色素瘤和PD之间的正的和显著的遗传相关性（相关性：0.17，95% CI 0.10-0.24; P = 4.09 x 10（-06））。我们进一步证明了黑色素瘤和PD推断的基因表达在组织中重叠（相关性：0.14，95% CI 0.06至0.22; P = 7.87 x 10（-04）），并强调了7个基因，包括PIEZO 1，TRAPPC 2L和SOX 6，作为黑色素瘤和PD之间遗传相关性的潜在介质。这些发现表明PD和黑色素瘤之间在基因表达水平上表现出特定的，共享的遗传结构。
Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10-0.24; P = 4.09 x 10(-06)) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 x 10(-04)) and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.