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Improving genetic prediction by leveraging genetic correlations among human diseases and traits

Authors :
Maier, R. M.
Zhu, Z.
Lee, S. H.
Trzaskowski, M.
Ruderfer, D. M.
Stahl, E. A.
Ripke, S.
Wray, N. R.
Yang, J.
Visscher, P. M.
Robinson, M. R.
Forstner, A. J.
Mcquillin, A.
Trubetskoy, V.
Wang, W.
Wang, Y.
Coleman, J. R. I.
Gaspar, H. A.
Leeuw, C. A.
Whitehead Pavlides, J. M.
Olde Loohuis, L. M.
Pers, T. H.
Lee, P. H.
Charney, A. W.
Dobbyn, A. L.
Huckins, L.
Boocock, J.
Giambartolomei, C.
Roussos, P.
Mullins, N.
Awasthi, S.
Agerbo, E.
Als, T. D.
Pedersen, C. B.
Grove, J.
Kupka, R.
Regeer, E. J.
Anjorin, A.
Casas, M.
Mahon, P. B.
Allardyce, J.
Escott-Price, V.
Forty, L.
Fraser, C.
Kogevinas, M.
Frank, J.
Streit, F.
Strohmaier, J.
Treutlein, J.
Witt, S. H.
Kennedy, J. L.
Strauss, J. S.
Garnham, J.
O Donovan, C.
Slaney, C.
Steinberg, S.
Thorgeirsson, T. E.
Hautzinger, M.
Steffens, M.
Perlis, R. H.
Sánchez-Mora, C.
Hipolito, M.
Lawson, W. B.
Nwulia, E. A.
Levy, S. E.
Foroud, T. M.
Jamain, S.
Young, A. H.
Mckay, J. D.
Albani, D.
Zandi, P.
Potash, J. B.
Zhang, P.
Raymond Depaulo, J.
Bergen, S. E.
Juréus, A.
Karlsson, R.
Kandaswamy, R.
Mcguffin, P.
Rivera, M.
Lissowska, J.
Cruceanu, C.
Lucae, S.
Cervantes, P.
Budde, M.
Gade, K.
Heilbronner, U.
Pedersen, M. G.
Morris, D. W.
Weickert, C. S.
Weickert, T. W.
Macintyre, D. J.
Lawrence, J.
Elvsåshagen, T.
Smeland, O. B.
Djurovic, S.
Xi, S.
Green, E. K.
Czerski, P. M.
Hauser, J.
Xu, W.
Vedder, H.
Oruc, L.
Spijker, A. T.
Gordon, S. D.
Medland, S. E.
Curtis, D.
Mühleisen, T. W.
Badner, J. A.
Scheftner, W. A.
Sigurdsson, E.
Schork, N. J.
Schatzberg, A. F.
Bækvad-Hansen, M.
Bybjerg-Grauholm, J.
Hansen, C. S.
Knowles, J. A.
Szelinger, S.
Montgomery, G. W.
Boks, M.
Adolfsson, A. N.
Hoffmann, P.
Bauer, M.
Pfennig, A.
Leber, M.
Kittel-Schneider, S.
Reif, A.
Del-Favero, J.
Fischer, S. B.
Herms, S.
Reinbold, C. S.
Degenhardt, F.
Koller, A. C.
Maaser, A.
Ori, A. P. S.
Dale, A. M.
Fan, C. C.
Greenwood, T. A.
Nievergelt, C. M.
Shehktman, T.
Shilling, P. D.
Byerley, W.
Bunney, W.
Alliey-Rodriguez, N.
Clarke, T. K.
Liu, C.
Coryell, W.
Akil, H.
Burmeister, M.
Flickinger, M.
Li, J. Z.
Mcinnis, M. G.
Meng, F.
Thompson, R. C.
Watson, S. J.
Zollner, S.
Guan, W.
Green, M. J.
Craig, D.
Sobell, J. L.
Milani, L.
Gordon-Smith, Katherine
Knott, Sarah
Perry, Amy
Parra, J. G.
Mayoral, F.
Rivas, F.
Rice, J. P.
Barchas, J. D.
Børglum, A. D.
Mortensen, P. B.
Mors, O.
Grigoroiu-Serbanescu, M.
Bellivier, F.
Etain, B.
Leboyer, M.
Ramos-Quiroga, J. A.
Agartz, I.
Amin, F.
Azevedo, M. H.
Bass, N.
Black, D. W.
Blackwood, D. H. R.
Bruggeman, R.
Buccola, N. G.
Choudhury, K.
Cloninger, C. R.
Corvin, A.
Craddock, N.
Daly, M. J.
Datta, S.
Donohoe, G. J.
Duan, J.
Dudbridge, F.
Fanous, A.
Freedman, R.
Freimer, N. B.
Friedl, M.
Gill, M.
Gurling, H.
Haan, L.
Hamshere, M. L.
Hartmann, A. M.
Holmans, P. A.
Kahn, R. S.
Keller, M. C.
Kenny, E.
Kirov, G. K.
Krabbendam, L.
Krasucki, R.
Lencz, T.
Levinson, D. F.
Lieberman, J. A.
Lin, D. -Y
Linszen, D. H.
Magnusson, P. K. E.
Maier, W.
Malhotra, A. K.
Mattheisen, M.
Mattingsdal, M.
Mccarroll, S. A.
Medeiros, H.
Melle, I.
Milanova, V.
Myin-Germeys, I.
Neale, B. M.
Ophoff, R. A.
Owen, M. J.
Pimm, J.
Purcell, S. M.
Puri, V.
Digby Quested
Rossin, L.
Sanders, A. R.
Shi, J.
Sklar, P.
St Clair, D.
Stroup, T. S.
Os, J.
Wiersma, D.
Zammit, S.
Maier, Robert M
Zhu, Zhihong
Lee, Sang Hong
Trzaskowski, Maciej
Ruderfer, Douglas M
Stahl, Eli A
Ripke, Stephan
Wray, Naomi R
Yang, Jian
Visscher, Peter M
Robinson, Matthew R
Bipolar Disorder Working Grp Psy
Schizophrenia Working Grp Psychiat
Complex Trait Genetics
Amsterdam Neuroscience - Complex Trait Genetics
APH - Mental Health
ANS - Complex Trait Genetics
Adult Psychiatry
Psychiatry
Source :
Nature Communications, Nature Communications, 9(1):02769-6. Nature Publishing Group, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J, Visscher, P M, Robinson, M R, Forstner, A J, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, J R I, Gaspar, H A, De Leeuw, C A, Whitehead Pavlides, J M, Olde Loohuis, L M, Pers, T H, Lee, P H, Charney, A W, Dobbyn, A L, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, T D, Pedersen, C B, Grove, J, Kupka, R, Regeer, E J, Anjorin, A, Casas, M, Mahon, P B, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J & Treutlein, J 2018, ' Improving genetic prediction by leveraging genetic correlations among human diseases and traits ', Nature Communications, vol. 9, no. 1, 02769-6 . https://doi.org/10.1038/s41467-017-02769-6, Nature Communications, 9(1). Nature Publishing Group, Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018), Nature communications, 9(1):02769-6. Nature Publishing Group, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J, Visscher, P M, Robinson, M R, Forstner, A J, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, J R I, Gaspar, H L A, de Leeuw, C A, Whitehead Pavlides, J M, Olde Loohuis, L M, Pers, T H, Lee, P H, Charney, A W, Dobbyn, A L, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, T D, Pedersen, C B C, Grove, J, Kupka, R, Regeer, E J, Anjorin, A, Casas, M, Mahon, P B, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J, Treutlein, J, Witt, S H, Kennedy, J L, Strauss, J S, Garnham, J, O'donovan, C, Slaney, C, Steinberg, S, Thorgeirsson, T E, Hautzinger, M, Steffens, M, Perlis, R H, Sánchez-Mora, C, Hipolito, M, Lawson, W B, Nwulia, E A, Levy, S E, Foroud, T M, Jamain, S, Young, A H, Mckay, J D, Albani, D, Zandi, P, Potash, J B, Zhang, P, Raymond Depaulo, J, Bergen, S E, Juréus, A, Karlsson, R, Kandaswamy, R, Mcguffin, P, Rivera, M, Lissowska, J, Cruceanu, C, Lucae, S, Cervantes, P, Budde, M, Gade, K, Heilbronner, U, Pedersen, M G, Morris, D W, Weickert, C S, Weickert, T W, Macintyre, D J, Lawrence, J, Elvsåshagen, T, Smeland, O B, Djurovic, S, Xi, S, Green, E K, Czerski, P M, Hauser, J, Xu, W, Vedder, H, Oruc, L, Spijker, A T, Gordon, S D, Medland, S E, Curtis, D, Mühleisen, T W, Badner, J, Scheftner, W A, Sigurdsson, E, Schork, N J, Schatzberg, A F, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, C S H, Knowles, J A, Szelinger, S, Montgomery, G W, Boks, M, Adolfsson, A N, Hoffmann, P, Bauer, M, Pfennig, A, Leber, M, Kittel-Schneider, S, Reif, A, del-Favero, J, Fischer, S B, Herms, S, Reinbold, C L S, Degenhardt, F, Koller, A C, Maaser, A, Ori, A, Dale, A M, Fan, C C, Greenwood, T A, Nievergelt, C M, Shehktman, T, Shilling, P D, Byerley, W, Bunney, W, Alliey-Rodriguez, N, Clarke, T-K, Liu, C, Coryell, W, Akil, H, Burmeister, M, Flickinger, M, Li, J Z, Mcinnis, M G, Meng, F, Thompson, R C, Watson, S J, Zollner, S, Guan, W, Green, M J, Craig, D, Sobell, J L, Milani, L, Gordon-Smith, K, Knott, S V, Perry, A, Parra, J G, Mayoral, F, Rivas, F, Rice, J P, Barchas, J D, Børglum, A D, Mortensen, P B, Mors, O, Grigoroiu-Serbanescu, M, Bellivier, F, Etain, B, Leboyer, M, Ramos-Quiroga, J A, Agartz, I, Amin, F, Azevedo, M H, Bass, N, Black, D W, Blackwood, D H R, Bruggeman, R, Buccola, N G, Choudhury, K, Cloninger, C R, Corvin, A, Craddock, N, Daly, M J, Datta, S, Donohoe, G J, Duan, J, Dudbridge, F, Fanous, A, Freedman, R, Freimer, N B, Friedl, M, Gill, M, Gurling, H, de Haan, L, Hamshere, M L, Hartmann, A M, Holmans, P A, Kahn, R S, Keller, M C, Kenny, E, Kirov, G K, Krabbendam, L, Krasucki, R, Lencz, T, Levinson, D F, Lieberman, J A, Lin, D-Y, Linszen, D H, Magnusson, P K E, Maier, W, Malhotra, A K, Mattheisen, M, Mattingsdal, M, Mccarroll, S A, Medeiros, H, Melle, I, Milanova, V, Myin-Germeys, I, Neale, B M, Ophoff, R A, Owen, M J, Pimm, J, Purcell, S M, Puri, V, Quested, D J, Rossin, L, Sanders, A R, Shi, J, Sklar, P, St Clair, D, Stroup, T S, van Os, J, Wiersma, D & Zammit, S 2018, ' Improving genetic prediction by leveraging genetic correlations among human diseases and traits ', Nature Communications, vol. 9, no. 1, 02769-6 . https://doi.org/10.1038/s41467-017-02769-6, Nature communications, vol. 9, no. 1, pp. 989, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J & Visscher, P M & Robinson, M R 2018, ' Improving genetic prediction by leveraging genetic correlations among human diseases and traits ', Nature Communications, vol. 9, no. 1, 989 . https://doi.org/10.1038/s41467-017-02769-6, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J, Visscher, P M, Robinson, M R, Forstner, A J, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, J R I, Gaspar, H A, De Leeuw, C A, Whitehead Pavlides, J M, Olde Loohuis, L M, Pers, T H, Lee, P H, Charney, A W, Dobbyn, A L, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, T D, Pedersen, C B, Grove, J, Kupka, R, Regeer, E J, Anjorin, A, Casas, M, Mahon, P B, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J, Treutlein, J, Witt, S H, Kennedy, J L, Strauss, J S, Garnham, J, O'donovan, C, Slaney, C, Steinberg, S, Thorgeirsson, T E, Hautzinger, M, Steffens, M, Perlis, R H, Sánchez-Mora, C, Hipolito, M, Lawson, W B, Nwulia, E A, Levy, S E, Foroud, T M, Jamain, S, Young, A H, Mckay, J D, Albani, D, Zandi, P, Potash, J B, Zhang, P, Raymond Depaulo, J, Bergen, S E, Juréus, A, Karlsson, R, Kandaswamy, R, Mcguffin, P, Rivera, M, Lissowska, J, Cruceanu, C, Lucae, S, Cervantes, P, Budde, M, Gade, K, Heilbronner, U, Pedersen, M G, Morris, D W, Weickert, C S, Weickert, T W, Macintyre, D J, Lawrence, J, Elvsåshagen, T, Smeland, O B, Djurovic, S, Xi, S, Green, E K, Czerski, P M, Hauser, J, Xu, W, Vedder, H, Oruc, L, Spijker, A T, Gordon, S D, Medland, S E, Curtis, D, Mühleisen, T W, Badner, J, Scheftner, W A, Sigurdsson, E, Schork, N J, Schatzberg, A F, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, C S, Knowles, J A, Szelinger, S, Montgomery, G W, Boks, M, Adolfsson, A N, Hoffmann, P, Bauer, M, Pfennig, A, Leber, M, Kittel-Schneider, S, Reif, A, Del-Favero, J, Fischer, S B, Herms, S, Reinbold, C S, Degenhardt, F, Koller, A C, Maaser, A, Ori, A, Dale, A M, Fan, C C, Greenwood, T A, Nievergelt, C M, Shehktman, T, Shilling, P D, Byerley, W, Bunney, W, Alliey-Rodriguez, N, Clarke, T K, Liu, C, Coryell, W, Akil, H, Burmeister, M, Flickinger, M, Li, J Z, Mcinnis, M G, Meng, F, Thompson, R C, Watson, S J, Zollner, S, Guan, W, Green, M J, Craig, D, Sobell, J L, Milani, L, Gordon-Smith, K, Knott, S V, Perry, A, Parra, J G, Mayoral, F, Rivas, F, Rice, J P, Barchas, J D, Børglum, A D, Mortensen, P B, Mors, O, Grigoroiu-Serbanescu, M, Bellivier, F, Etain, B, Leboyer, M, Ramos-Quiroga, J A, Agartz, I, Amin, F, Azevedo, M H, Bass, N, Black, D W, Blackwood, D H R, Bruggeman, R, Buccola, N G, Choudhury, K, Cloninger, C R, Corvin, A, Craddock, N, Daly, M J, Datta, S, Donohoe, G J, Duan, J, Dudbridge, F, Fanous, A, Freedman, R, Freimer, N B, Friedl, M, Gill, M, Gurling, H, De Haan, L, Hamshere, M L, Hartmann, A M, Holmans, P A, Kahn, R S, Keller, M C, Kenny, E, Kirov, G K, Krabbendam, L, Krasucki, R, Lencz, T, Levinson, D F, Lieberman, J A, Lin, D Y, Linszen, D H, Magnusson, P K E, Maier, W, Malhotra, A K, Mattheisen, M, Mattingsdal, M, Mccarroll, S A, Medeiros, H, Melle, I, Milanova, V, Myin-Germeys, I, Neale, B M, Ophoff, R A, Owen, M J, Pimm, J, Purcell, S M, Puri, V, Quested, D J, Rossin, L, Sanders, A R, Shi, J, Sklar, P, St Clair, D, Stroup, T S, Van Os, J, Wiersma, D & Zammit, S 2018, ' Improving genetic prediction by leveraging genetic correlations among human diseases and traits ', Nature Communications, vol. 9, no. 1, 02769-6 . https://doi.org/10.1038/s41467-017-02769-6, BASE-Bielefeld Academic Search Engine
Publication Year :
2018
Publisher :
Springer Science and Business Media LLC, 2018.

Abstract

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait.<br />Genetic prediction of complex traits so far has limited accuracy because of insufficient understanding of the genetic risk. Here, Maier et al. develop an improved method for trait prediction that makes use of genetic correlations between traits and apply it to summary statistics of psychiatric diseases.

Details

Language :
English
ISSN :
20411723
Database :
OpenAIRE
Journal :
Nature Communications, Nature Communications, 9(1):02769-6. Nature Publishing Group, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J, Visscher, P M, Robinson, M R, Forstner, A J, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, J R I, Gaspar, H A, De Leeuw, C A, Whitehead Pavlides, J M, Olde Loohuis, L M, Pers, T H, Lee, P H, Charney, A W, Dobbyn, A L, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, T D, Pedersen, C B, Grove, J, Kupka, R, Regeer, E J, Anjorin, A, Casas, M, Mahon, P B, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J & Treutlein, J 2018, ' Improving genetic prediction by leveraging genetic correlations among human diseases and traits ', Nature Communications, vol. 9, no. 1, 02769-6 . https://doi.org/10.1038/s41467-017-02769-6, Nature Communications, 9(1). Nature Publishing Group, Nature Communications, Vol 9, Iss 1, Pp 1-17 (2018), Nature communications, 9(1):02769-6. Nature Publishing Group, Maier, R M, Zhu, Z, Lee, S H, Trzaskowski, M, Ruderfer, D M, Stahl, E A, Ripke, S, Wray, N R, Yang, J, Visscher, P M, Robinson, M R, Forstner, A J, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, J R I, Gaspar, H L A, de Leeuw, C A, Whitehead Pavlides, J M, Olde Loohuis, L M, Pers, T H, Lee, P H, Charney, A W, Dobbyn, A L, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, T D, Pedersen, C B C, Grove, J, Kupka, R, Regeer, E J, Anjorin, A, Casas, M, Mahon, P B, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J, Treutlein, J, Witt, S H, Kennedy, J L, Strauss, J S, Garnham, J, O'donovan, C, Slaney, C, Steinberg, S, Thorgeirsson, T E, Hautzinger, M, Steffens, M, Perlis, R H, Sánchez-Mora, C, Hipolito, M, Lawson, W B, Nwulia, E A, Levy, S E, Foroud, T M, Jamain, S, Young, A H, Mckay, J D, Albani, D, Zandi, P, Potash, J B, Zhang, P, Raymond Depaulo, J, Bergen, S E, Juréus, A, Karlsson, R, Kandaswamy, R, Mcguffin, P, Rivera, M, Lissowska, J, Cruceanu, C, Lucae, S, Cervantes, P, Budde, M, Gade, K, Heilbronner, U, Pedersen, M G, Morris, D W, Weickert, C S, Weickert, T W, Macintyre, D J, Lawrence, J, Elvsåshagen, T, Smeland, O B, Djurovic, S, Xi, S, Green, E K, Czerski, P M, Hauser, J, Xu, W, Vedder, H, Oruc, L, Spijker, A T, Gordon, S D, Medland, S E, Curtis, D, Mühleisen, T W, Badner, J, Scheftner, W A, Sigurdsson, E, Schork, N J, Schatzberg, A F, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, C S H, Knowles, J A, Szelinger, S, Montgomery, G W, Boks, M, Adolfsson, A N, Hoffmann, P, Bauer, M, Pfennig, A, Leber, M, Kittel-Schneider, S, Reif, A, del-Favero, J, Fischer, S B, Herms, S, Reinbold, C L S, Degenhardt, F, Koller, A C, Maaser, A, Ori, A, Dale, A M, Fan, C C, Greenwood, T A, Nievergelt, C M, Shehktman, T, Shilling, P D, Byerley, W, Bunney, W, Alliey-Rodriguez, N, Clarke, T-K, Liu, C, Coryell, W, Akil, H, Burmeister, M, Flickinger, M, Li, J Z, Mcinnis, M G, Meng, F, Thompson, R C, Watson, S J, Zollner, S, Guan, W, Green, M J, Craig, D, Sobell, J L, Milani, L, Gordon-Smith, K, Knott, S V, Perry, A, Parra, J G, Mayoral, F, Rivas, F, Rice, J P, Barchas, J D, Børglum, A D, Mortensen, P B, Mors, O, Grigoroiu-Serbanescu, M, Bellivier, F, Etain, B, Leboyer, M, Ramos-Quiroga, J A, Agartz, I, Amin, F, Azevedo, M H, Bass, N, Black, D W, Blackwood, D H R, Bruggeman, R, Buccola, N G, Choudhury, K, Cloninger, C R, Corvin, A, Craddock, N, Daly, M J, Datta, S, Donohoe, G J, Duan, J, Dudbridge, F, Fanous, A, Freedman, R, Freimer, N B, Friedl, M, Gill, M, Gurling, H, de Haan, L, Hamshere, M L, Hartmann, A M, Holmans, P A, Kahn, R S, Keller, M C, Kenny, E, Kirov, G K, Krabbendam, L, Krasucki, R, Lencz, T, Levinson, D F, Lieberman, J A, Lin, D-Y, Linszen, D H, Magnusson, P K E, Maier, W, Malhotra, A K, Mattheisen, M, Mattingsdal, M, Mccarroll, S A, Medeiros, H, Melle, I, Milanova, V, Myin-Germeys, I, Neale, B M, Ophoff, R A, Owen, M J, Pimm, 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