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2. Overlapping genetic architecture between Parkinson disease and melanoma

Author

Dube, Umber Ibanez, Laura Budde, John P. Benitez, Bruno A. and Davis, Albert A. Harari, Oscar Iles, Mark M. Law, Matthew H. Brown, Kevin M. Agee, Michelle Alipanahi, Babak and Auton, Adam Bell, Robert K. Bryc, Katarzyna Elson, Sarah L. Fontanillas, Pierre Furlotte, Nicholas A. Hinds, David A. and Huber, Karen E. Kleinman, Aaron Litterman, Nadia K. and McCreight, Jennifer C. McIntyre, Matthew H. Mountain, Joanna L. and Noblin, Elizabeth S. Northover, Carrie A. M. Pitts, Steven J. Sathirapongsasuti, J. Fah Sazonova, Olga V. Shelton, Janie F. Shringarpure, Suyash Tian, Chao Tung, Joyce Y. and Vacic, Vladimir Wilson, Catherine H. Law, M. H. Law, M. H. and Bishop, D. T. Lee, J. E. Brossard, M. Martin, N. G. and Moses, E. K. Song, F. Barrett, J. H. Kumar, R. Easton, D. F. Pharoah, P. D. Swerdlow, A. J. Kypreou, K. P. and Taylor, J. C. Harland, M. Randerson-Moor, J. Akslen, L. A. and Andresen, P. A. Avril, M. F. Azizi, E. Scarra, G. B. and Brown, K. M. Debniak, T. Duffy, D. L. Elder, D. E. Fang, S. Friedman, E. Galan, P. Ghiorzo, P. Gillanders, E. M. and Goldstein, A. M. Gruis, N. A. Hansson, J. Helsing, P. and Hocevar, M. Hoiom, V. Ingvar, C. Kanetsky, P. A. and Chen, W. V. Landi, M. T. Lang, J. Lathrop, G. M. and Lubinski, J. Mackie, R. M. Mann, G. J. Molven, A. and Montgomery, G. W. Novakovic, S. Olsson, H. Puig, S. and Puig-Butille, J. A. Wu, W. Qureshi, A. A. Radford-Smith, G. L. Van der Stoep, N. Van Doorn, R. Whiteman, D. C. and Craig, J. E. Schadendorf, E. Simms, L. A. Burdon, K. P. and Nyholt, D. R. Pooley, K. A. Orr, N. Stratigos, A. J. and Cust, A. E. Ward, S. V. Hayward, N. K. Han, J. Schulze, H. J. Dunning, A. M. Bishop, J. A. Demenais, F. Amos, C. I. MacGregor, S. Iles, M. M. Cruchaga, Carlos 23andMe Research Team Melanoma Meta Analysis Consortium

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 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.

Published
2020

3. Overlapping genetic architecture between Parkinson disease and melanoma

Author

Dube, Umber, Ibanez, Laura, Budde, John P., Benitez, Bruno A., Davis, Albert A., Harari, Oscar, Iles, M. M., Law, Matthew H., Brown, Kevin M., Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hinds, David A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Bishop, D. T., Lee, J. E., Brossard, M., Martin, N. G., Moses, E. K., Song, F., Barrett, J. H., Kumar, R., Easton, D. F., Pharoah, P. D., Swerdlow, A. J., Kypreou, K. P., Taylor, J. C., Harland, M., Randerson-Moor, J., Akslen, L. A., Andresen, P. A., Avril, M. F., Azizi, E., Scarrà, G. B., Brown, K. M., Debniak, T., Duffy, D. L., Elder, D. E., Fang, S., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E. M., Goldstein, A. M., Gruis, N. A., Hansson, J., Helsing, P., Hočevar, M., Höiom, V., Ingvar, C., Kanetsky, P. A., Chen, W. V., Landi, M. T., Lang, J., Lathrop, G. M., Lubiński, J., Mackie, R. M., Mann, G. J., Molven, A., Montgomery, G. W., Novaković, S., Olsson, H., Puig, S., Puig-Butille, J. A., Wu, W., Qureshi, A. A., Radford-Smith, G. L., van der Stoep, N., van Doorn, R., Whiteman, D. C., Craig, J. E., Schadendorf, E., Simms, L. A., Burdon, K. P., Nyholt, D. R., Pooley, K. A., Orr, N., Stratigos, A. J., Cust, A. E., Ward, S. V., Hayward, N. K., Han, J., Schulze, H. J., Dunning, A. M., Bishop, J. A., Demenais, F., Amos, C. I., MacGregor, S., Cruchaga, Carlos, other, and, Dube, Umber, Ibanez, Laura, Budde, John P., Benitez, Bruno A., Davis, Albert A., Harari, Oscar, Iles, M. M., Law, Matthew H., Brown, Kevin M., Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Hinds, David A., Huber, Karen E., Kleinman, Aaron, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Bishop, D. T., Lee, J. E., Brossard, M., Martin, N. G., Moses, E. K., Song, F., Barrett, J. H., Kumar, R., Easton, D. F., Pharoah, P. D., Swerdlow, A. J., Kypreou, K. P., Taylor, J. C., Harland, M., Randerson-Moor, J., Akslen, L. A., Andresen, P. A., Avril, M. F., Azizi, E., Scarrà, G. B., Brown, K. M., Debniak, T., Duffy, D. L., Elder, D. E., Fang, S., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E. M., Goldstein, A. M., Gruis, N. A., Hansson, J., Helsing, P., Hočevar, M., Höiom, V., Ingvar, C., Kanetsky, P. A., Chen, W. V., Landi, M. T., Lang, J., Lathrop, G. M., Lubiński, J., Mackie, R. M., Mann, G. J., Molven, A., Montgomery, G. W., Novaković, S., Olsson, H., Puig, S., Puig-Butille, J. A., Wu, W., Qureshi, A. A., Radford-Smith, G. L., van der Stoep, N., van Doorn, R., Whiteman, D. C., Craig, J. E., Schadendorf, E., Simms, L. A., Burdon, K. P., Nyholt, D. R., Pooley, K. A., Orr, N., Stratigos, A. J., Cust, A. E., Ward, S. V., Hayward, N. K., Han, J., Schulze, H. J., Dunning, A. M., Bishop, J. A., Demenais, F., Amos, C. I., MacGregor, S., Cruchaga, Carlos, and other, and

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.

Published
2020

4. Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study

Author

Demenais, F., Mohamdi, H., Chaudru, V., Goldstein, A. M., Newton Bishop, J. A., Bishop, D. T., Kanetsky, P. A., Hayward, N. K., Gillanders, E., Elder, D. E., Avril, M. F., Azizi, E., van Belle, P., Bergman, W., Bianchi-Scarrà, G., Bressac-de Paillerets, B., Calista, D., Carrera, C., Hansson, J., Harland, M., Hogg, D., Höiom, V., Holland, E. A., Ingvar, C., Landi, M. T., Lang, J. M., Mackie, R. M., Mann, G. J., Ming, M. E., Njauw, C. J., Olsson, H., Palmer, J., Pastorino, L., Puig, S., Randerson-Moor, J., Stark, M., Tsao, H., Tucker, M. A., van der Velden, P., Yang, X. R., and Gruis, N.

Published
2010
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9. Overlapping genetic architecture between Parkinson disease and melanoma

Author

Dube, U., Ibanez, L., Budde, J. P., Benitez, B. A., Davis, A. A., Harari, O., Iles, M. M., Law, M. H., Brown, K. M., Agee, M., Alipanahi, B., Auton, A., Bell, R. K., Bryc, K., Elson, S. L., Fontanillas, P., Furlotte, N. A., Hinds, D. A., Huber, K. E., Kleinman, A., Litterman, N. K., Mccreight, J. C., Mcintyre, M. H., Mountain, J. L., Noblin, E. S., Northover, C. A. M., Pitts, S. J., Sathirapongsasuti, J. F., Sazonova, O. V., Shelton, J. F., Shringarpure, S., Tian, C., Tung, J. Y., Vacic, V., Wilson, C. H., Bishop, D. T., Lee, J. E., Brossard, M., Martin, N. G., Moses, E. K., Song, F., Barrett, J. H., Kumar, R., Easton, D. F., Pharoah, P. D., Swerdlow, A. J., Kypreou, K. P., Taylor, J. C., Harland, M., Randerson-Moor, J., Akslen, L. A., Andresen, P. A., Avril, M. F., Azizi, E., Scarra, G. B., Debniak, T., Duffy, D. L., Elder, D. E., Fang, S., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E. M., Goldstein, A. M., Gruis, N. A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Ingvar, C., Kanetsky, P. A., Chen, W. V., Landi, M. T., Lang, J., Lathrop, G. M., Lubinski, J., Mackie, R. M., Mann, G. J., Molven, A., Montgomery, G. W., Novakovic, S., Olsson, H., Puig, S., Puig-Butille, J. A., Wu, W., Qureshi, A. A., Radford-Smith, G. L., van der Stoep, N., van Doorn, R., Whiteman, D. C., Craig, J. E., Schadendorf, E., Simms, L. A., Burdon, K. P., Nyholt, D. R., Pooley, K. A., Orr, N., Stratigos, A. J., Cust, A. E., Ward, S. V., Hayward, N. K., Han, J., Schulze, H. J., Dunning, A. M., Bishop, J. A., Demenais, F., Amos, C. I., Macgregor, S., and Cruchaga, C.

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Genetic correlation, Multifactorial Inheritance, Skin Neoplasms, Medizin, TWAS, Disease, Melanoma, Parkinson disease, Polygenic, Shared genetic architecture, Pathology and Forensic Medicine, Correlation, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, Gene expression, Medicine, Humans, Gene, business.industry, Parkinson Disease, medicine.disease, Genetic architecture, 030104 developmental biology, Case-Control Studies, Cutaneous melanoma, Neurology (clinical), business, 030217 neurology & neurosurgery, Genome-Wide Association Study
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 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.

Published
2019

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