TY - JOUR
T1 - Overlapping genetic architecture between Parkinson disease and melanoma
AU - GenoMEL Consortium
AU - Essen-Heidelberg Investigators
AU - SDH Study Group
AU - Q-MEGA and QTWIN Investigators
AU - AMFS Investigators
AU - ATHENS Melanoma Study Group
AU - Melanoma-Meta-analysis Consortium
AU - 23andMe Research Team
AU - Dube, Umber
AU - Ibanez, Laura
AU - Budde, John P.
AU - Benitez, Bruno A.
AU - Davis, Albert A.
AU - Harari, Oscar
AU - Iles, Mark M.
AU - Law, Matthew H.
AU - Brown, Kevin M.
AU - Agee, Michelle
AU - Alipanahi, Babak
AU - Auton, Adam
AU - Bell, Robert K.
AU - Bryc, Katarzyna
AU - Elson, Sarah L.
AU - Fontanillas, Pierre
AU - Furlotte, Nicholas A.
AU - Hinds, David A.
AU - Huber, Karen E.
AU - Kleinman, Aaron
AU - Litterman, Nadia K.
AU - McCreight, Jennifer C.
AU - McIntyre, Matthew H.
AU - Mountain, Joanna L.
AU - Noblin, Elizabeth S.
AU - Northover, Carrie A.M.
AU - Pitts, Steven J.
AU - Sathirapongsasuti, J. Fah
AU - Sazonova, Olga V.
AU - Shelton, Janie F.
AU - Shringarpure, Suyash
AU - Tian, Chao
AU - Tung, Joyce Y.
AU - Vacic, Vladimir
AU - Wilson, Catherine H.
AU - Bishop, D. T.
AU - Lee, J. E.
AU - Brossard, M.
AU - Martin, N. G.
AU - Moses, E. K.
AU - Song, F.
AU - Barrett, J. H.
AU - Kumar, R.
AU - Easton, D. F.
AU - Pharoah, P. D.
AU - Swerdlow, A. J.
AU - Kypreou, K. P.
AU - Taylor, J. C.
AU - Azizi, E.
AU - Friedman, E.
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - Genetic correlation
KW - Melanoma
KW - Parkinson disease
KW - Polygenic
KW - Shared genetic architecture
KW - TWAS
UR - http://www.scopus.com/inward/record.url?scp=85076915423&partnerID=8YFLogxK
U2 - 10.1007/s00401-019-02110-z
DO - 10.1007/s00401-019-02110-z
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C2 - 31845298
AN - SCOPUS:85076915423
SN - 0001-6322
VL - 139
SP - 347
EP - 364
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 2
ER -
