Journal
ACTA NEUROPATHOLOGICA
Volume 139, Issue 2, Pages 347-364Publisher
SPRINGER
DOI: 10.1007/s00401-019-02110-z
Keywords
Parkinson disease; Melanoma; Genetic correlation; Polygenic; TWAS; Shared genetic architecture
Categories
Funding
- National Institutes of Health [R01AG044546, P01AG003991, RF1AG053303, R01AG058501, U01AG058922, K01AG046374, K08NS101118, R01HL119813]
- Alzheimer Association [IRG-11-200110, BAND-14-338165, AARG-16-441560, BFG-15-362540, ADGC-10-196728]
- Hope Center for Neurological Disorders
- Departments of Neurology and Psychiatry at Washington University School of Medicine
- French National Foundation on Alzheimer disease and related disorders
- LABEX (laboratory of excellence program investment for the future)
- DISTALZ grant
- Inserm
- Institut Pasteur de Lille
- Universite de Lille 2
- Lille University Hospital
- Medical Research Council [503480]
- Alzheimer Research UK [503176]
- Wellcome Trust [082604/2/07/Z]
- German Federal Ministry of Education and Research (BMBF)
- Competence Network Dementia (CND) [01GI0102, 01GI0711, 01GI0420]
- NIH/NIA grant [R01 AG033193]
- NIA [AG081220]
- AGES contract [N01-AG-12100]
- NHLBI grant [R01 HL105756]
- Icelandic Heart Association
- Erasmus Medical Center
- Erasmus University
- NIH/NIA grants [U01 AG032984, U24 AG021886, U01 AG016976]
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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.
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