Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

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R., Farh, Kai-How, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa ORCID: https://orcid.org/0000-0003-0739-0382, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C. K., Chan, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Cheung, Eric F. 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R., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Owen, Michael J ORCID: https://orcid.org/0000-0003-4798-0862, Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F. and O'Donovan, Michael C ORCID: https://orcid.org/0000-0001-7073-2379 2017. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nature Communications 8 , 14774. 10.1038/ncomms14774

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Abstract

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P¼1�10�4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P¼8.4�10�7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium Marian L. Hamshere is a member of the Schizophrenia Working Group of the Psychiatric Genomics Consortium
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	20 April 2017
Date of Acceptance:	3 February 2017
Last Modified:	20 Oct 2023 06:25
URI:	https://orca.cardiff.ac.uk/id/eprint/99991

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