Overlapping genetic architecture between Parkinson disease and melanoma

Umber Dube, Laura Ibanez, John P. Budde, Bruno A. Benitez, Albert A. Davis, Oscar Harari, M. M. Iles, M. H. Law, Kevin M. Brown, Carlos Cruchaga, 23andMe Research Team, Melanoma-Meta-analysis Consortium, R. Kumar, GenoMEL Consortium, Essen-Heidelberg Investigators, SDH Study Group, Q-MEGA and QTWIN Investigators, AMFS Investigators, ATHENS Melanoma Study Group, J. E. CraigK. P. Burdon

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)347-364
Number of pages18
JournalActa Neuropathologica
Volume139
Issue number2
Early online date16 Dec 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Genetic correlation
  • Melanoma
  • Parkinson disease
  • Polygenic
  • Shared genetic architecture
  • TWAS

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