Open AccessOverlapping genetic architecture between Parkinson disease and melanoma
Author(s) -
Umber Dube,
Laura Ibáñez,
John Budde,
Bruno A. Benítez,
Albert A. Davis,
Oscar Harari,
Mark M. Iles,
Matthew Law,
Kevin M. Brown,
Carlos Cruchaga
Publication year - 2019
Publication title -
acta neuropathologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.183
H-Index - 170
eISSN - 1432-0533
pISSN - 0001-6322
DOI - 10.1007/s00401-019-02110-z
Subject(s) - melanoma , genetic architecture , linkage disequilibrium , genetic association , genome wide association study , disease , correlation , biology , genetic correlation , genetics , gene , genetic variation , genotype , medicine , single nucleotide polymorphism , quantitative trait locus , geometry , mathematics
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 × 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 × 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.