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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Lee, S., Ripke, S., Neale, B., Faraone, S., Purcell, S., Perlis, R., Mowry, B., Thapar, Anita, Goddard, M., Witte, J., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O., Anjorin, A., Anney, Richard, Anttila, V., Arking, D., Asherson, P., Azevedo, M., Backlund, L., Badner, J., Bailey, A., Banaschewski, T., Barchas, J., Barnes, M., Barrett, T., Bass, N., Battaglia, A., Bauer, M., Bayés, M., Bellivier, F., Bergen, S., Berrettini, W., Betancur, C., Bettecken, T., Biederman, J., Binder, E., Black, D., Blackwood, D., Bloss, C., Boehnke, M., Boomsma, D., Breen, G., Breuer, R., Bruggeman, R., Cormican, P., Buccola, N., Buitelaar, J., Bunney, W., Buxbaum, J., Byerley, W., Byrne, E., Caesar, S., Cahn, W., Cantor, R., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Cloninger, C., Collier, D., Cook, E., Coon, H., Cormand, B., Corvin, A., Coryell, W., Craig, D., Craig, I., Crosbie, J., Cuccaro, M., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., De Geus, E., Degenhardt, F., Djurovic, S., Donohoe, G., Doyle, A., Duan, J., Dudbridge, F., Duketis, E., Ebstein, R., Edenberg, H., Elia, J., Ennis, S., Etain, B., Fanous, A., Farmer, A., Ferrier, I., Flickinger, M., Fombonne, E., Foroud, T., Frank, J., Franke, B., Fraser, Christine, Freedman, R., Freimer, N., Freitag, C., Friedl, M., Frisén, L., Gallagher, L., Gejman, P., Georgieva, Lyudmila, Gershon, E., Geschwind, D., Giegling, I., Gill, M., Gordon, S., Gordon-Smith, K., Green, E., Greenwood, T., Grice, D., Gross, M., Grozeva, D., Guan, W., Gurling, H., De Haan, L., Haines, J., Hakonarson, H., Hallmayer, J., Hamilton, S., Hamshere, Marian Lindsay, Hansen, T., Hartmann, A., Hautzinger, M., Heath, A., Henders, A., Herms, S., Hickie, I., Hipolito, M., Hoefels, S., Holmans, Peter Alan, Holsboer, F., Hoogendijk, W., Hottenga, J., Hultman, C., Hus, V., Ingason, A., Ising, M., Jamain, S., Jones, E., Jones, Ian Richard, Jones, L., Tzeng, J., Kähler, A., Kahn, R., Kandaswamy, R., Keller, M., Kennedy, J., Kenny, E., Kent, L., Kim, Y., Kirov, George, Klauck, S., Klei, L., Knowles, J., Kohli, M., Koller, D., Konte, B., Korszun, A., Krabbendam, L., Krasucki, R., Kuntsi, J., Kwan, P., Landén, M., Långström, N., Lathrop, M., Lawrence, J., Lawson, W., Leboyer, M., Ledbetter, D., Lee, P., Lencz, T., Lesch, K., Levinson, D., Lewis, C., Li, J., Lichtenstein, P., Lieberman, J., Lin, D., Linszen, D., Liu, C., Lohoff, F., Loo, S., Lord, C., Lowe, J., Lucae, S., MacIntyre, D., Madden, P., Maestrini, E., Magnusson, P., Mahon, P., Maier, W., Malhotra, A., Mane, S., Martin, C., Martin, N., Mattheisen, M., Matthews, K., Mattingsdal, M., McCarroll, S., McGhee, K., McGough, J., McGrath, P., McGuffin, P., McInnis, M., McIntosh, A., McKinney, R., McLean, A., McMahon, F., McMahon, W., McQuillin, A., Medeiros, H., Medland, S., Meier, S., Melle, I., Meng, F., Meyer, J., Middeldorp, C., Middleton, L., Milanova, V., Miranda, A., Monaco, A., Montgomery, G., Moran, J., Moreno-De-Luca, D., Morken, G., Morris, D., Morrow, E., Moskvina, V., Muglia, P., Mühleisen, T., Muir, W., Müller-Myhsok, B., Murtha, M., Myers, R., Myin-Germeys, I., Neale, M., Nelson, S., Nievergelt, C., Nikolov, I., Nimgaonkar, V., Nolen, W., Nöthen, M., Nurnberger, J., Nwulia, E., Nyholt, D., O'Dushlaine, C., Oades, R., Olincy, A., Oliveira, G., Olsen, L., Ophoff, R., Osby, U., Owen, Michael John, Palotie, A., Parr, J., Paterson, A., Pato, C., Pato, M., Penninx, B., Pergadia, M., Pericak-Vance, M., Pickard, B., Pimm, J., Piven, J., Posthuma, D., Potash, J., Poustka, F., Propping, P., Puri, V., Quested, D., Quinn, E., Ramos-Quiroga, J., Rasmussen, H., Raychaudhuri, S., Rehnström, K., Reif, A., Ribasés, M., Rice, J., Rietschel, M., Roeder, K., Roeyers, H., Rossin, L., Rothenberger, A., Rouleau, G., Ruderfer, D., Rujescu, D., Sanders, A., Sanders, S., Santangelo, S., Sergeant, J., Schachar, R., Schalling, M., Schatzberg, A., Scheftner, W., Schellenberg, G., Scherer, S., Schork, N., Schulze, T., Schumacher, J., Schwarz, M., Scolnick, E., Scott, L., Shi, J., Shilling, P., Shyn, S., Silverman, J., Slager, S., Smalley, S., Smit, J., Smith, E., Sonuga-Barke, E., St. Clair, D., State, M., Steffens, M., Steinhausen, H., Strauss, J., Strohmaier, J., Stroup, T., Sutcliffe, J., Szatmari, P., Szelinger, S., Thirumalai, S., Thompson, R., Todorov, A., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E., Van Grootheest, G., Van Os, J., Vicente, A., Vieland, V., Vincent, J., Visscher, P., Walsh, C., Wassink, T., Watson, S., Weissman, M., Werge, T., Wienker, T., Wijsman, E., Willemsen, G., Williams, Nigel Melville, Willsey, A., Witt, S., Xu, W., Young, A., Yu, T., Zammit, Stanley, Zandi, P., Zhang, P., Zitman, F., Zöllner, S., Devlin, B., Kelsoe, J., Sklar, P., Daly, M., O'Donovan, Michael Conlon, Craddock, Nicholas John, Sullivan, P., Smoller, J., Kendler, K., Wray, N. and Escott-Price, Valentina 2013. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45 (9) , pp. 984-994. 10.1038/ng.2711

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Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Adult; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Crohn Disease; Depressive Disorder, Major; Genetic Heterogeneity; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Humans; Inheritance Patterns; Mental Disorders; Polymorphism, Single Nucleotide; Schizophrenia
Publisher: Nature Publishing Group
ISSN: 1061-4036
Date of Acceptance: 28 June 2013
Last Modified: 20 May 2019 21:28
URI: http://orca.cf.ac.uk/id/eprint/75680

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