Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Amelie Baud; Roel Hermsen; Victor Guryev; Pernilla Stridh; Delyth Graham; Martin W. McBride; Tatiana Foroud; Sophie Calderari; Margarita Diez; Johan Ockinger; Amennai D. Beyeen; Alan Gillett; Nada Abdelmagid; Andre Ortlieb Guerreiro-Cacais; Maja Jagodic; Jonatan Tuncel; Ulrika Norin; Elisabeth Beattie; Ngan Huynh; William H. Miller; Daniel L. Koller; Imranul Alam; Samreen Falak; Mary Osborne-Pellegrin; Esther Martinez-Membrives; Toni Canete; Gloria Blazquez; Elia Vicens-Costa; Carme Mont-Cardona; Sira Diaz-Moran; Adolf Tobena; Oliver Hummel; Diana Zelenika; Kathrin Saar; Giannino Patone; Anja Bauerfeind; Marie Therese Bihoreau; Matthias Heinig; Young Ae Lee; Carola Rintisch; Herbert Schulz; David A. Wheeler; Kim C. Worley; Donna M. Muzny; Richard A. Gibbs; Mark Lathrop; Nico Lansu; Pim Toonen; Frans Paul Ruzius; Ewart De Bruijn; Heidi Hauser; David J. Adams; Thomas Keane; Santosh S. Atanur; Tim J. Aitman; Paul Flicek; Tomas Malinauskas; E. Yvonne Jones; Diana Ekman; Regina Lopez-Aumatell; Anna F. Dominiczak; Martina Johannesson; Rikard Holmdahl; Tomas Olsson; Dominique Gauguier; Norbert Hubner; Alberto Fernandez-Teruel; Edwin Cuppen; Richard Mott; Jonathan Flint

doi:https://doi.org/10.1038/ng.2644

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Amelie Baud, Roel Hermsen, Victor Guryev, Pernilla Stridh, Delyth Graham, Martin W. McBride, Tatiana Foroud, Sophie Calderari, Margarita Diez, Johan Ockinger, Amennai D. Beyeen, Alan Gillett, Nada Abdelmagid, Andre Ortlieb Guerreiro-Cacais, Maja Jagodic, Jonatan Tuncel, Ulrika Norin, Elisabeth Beattie, Ngan Huynh, William H. MillerDaniel L. Koller, Imranul Alam, Samreen Falak, Mary Osborne-Pellegrin, Esther Martinez-Membrives, Toni Canete, Gloria Blazquez, Elia Vicens-Costa, Carme Mont-Cardona, Sira Diaz-Moran, Adolf Tobena, Oliver Hummel, Diana Zelenika, Kathrin Saar, Giannino Patone, Anja Bauerfeind, Marie Therese Bihoreau, Matthias Heinig, Young Ae Lee, Carola Rintisch, Herbert Schulz, David A. Wheeler, Kim C. Worley, Donna M. Muzny, Richard A. Gibbs, Mark Lathrop, Nico Lansu, Pim Toonen, Frans Paul Ruzius, Ewart De Bruijn, Heidi Hauser, David J. Adams, Thomas Keane, Santosh S. Atanur, Tim J. Aitman, Paul Flicek, Tomas Malinauskas, E. Yvonne Jones, Diana Ekman, Regina Lopez-Aumatell, Anna F. Dominiczak, Martina Johannesson, Rikard Holmdahl, Tomas Olsson, Dominique Gauguier, Norbert Hubner, Alberto Fernandez-Teruel, Edwin Cuppen, Richard Mott, Jonathan Flint

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131 Citations (Scopus)

Abstract

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species. © 2013 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	767-775
Journal	Nature Genetics
Volume	45
DOIs	https://doi.org/10.1038/ng.2644
Publication status	Published - 1 Jan 2013

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Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M. W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A. D., Gillett, A., Abdelmagid, N., Guerreiro-Cacais, A. O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., ... Flint, J. (2013). Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nature Genetics, 45, 767-775. https://doi.org/10.1038/ng.2644

@article{582d82e71ec04bd5a6ef298eb3789018,

title = "Combined sequence-based and genetic mapping analysis of complex traits in outbred rats",

abstract = "Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species. {\textcopyright} 2013 Nature America, Inc. All rights reserved.",

author = "Amelie Baud and Roel Hermsen and Victor Guryev and Pernilla Stridh and Delyth Graham and McBride, {Martin W.} and Tatiana Foroud and Sophie Calderari and Margarita Diez and Johan Ockinger and Beyeen, {Amennai D.} and Alan Gillett and Nada Abdelmagid and Guerreiro-Cacais, {Andre Ortlieb} and Maja Jagodic and Jonatan Tuncel and Ulrika Norin and Elisabeth Beattie and Ngan Huynh and Miller, {William H.} and Koller, {Daniel L.} and Imranul Alam and Samreen Falak and Mary Osborne-Pellegrin and Esther Martinez-Membrives and Toni Canete and Gloria Blazquez and Elia Vicens-Costa and Carme Mont-Cardona and Sira Diaz-Moran and Adolf Tobena and Oliver Hummel and Diana Zelenika and Kathrin Saar and Giannino Patone and Anja Bauerfeind and Bihoreau, {Marie Therese} and Matthias Heinig and Lee, {Young Ae} and Carola Rintisch and Herbert Schulz and Wheeler, {David A.} and Worley, {Kim C.} and Muzny, {Donna M.} and Gibbs, {Richard A.} and Mark Lathrop and Nico Lansu and Pim Toonen and Ruzius, {Frans Paul} and {De Bruijn}, Ewart and Heidi Hauser and Adams, {David J.} and Thomas Keane and Atanur, {Santosh S.} and Aitman, {Tim J.} and Paul Flicek and Tomas Malinauskas and Jones, {E. Yvonne} and Diana Ekman and Regina Lopez-Aumatell and Dominiczak, {Anna F.} and Martina Johannesson and Rikard Holmdahl and Tomas Olsson and Dominique Gauguier and Norbert Hubner and Alberto Fernandez-Teruel and Edwin Cuppen and Richard Mott and Jonathan Flint",

year = "2013",

month = jan,

day = "1",

doi = "https://doi.org/10.1038/ng.2644",

language = "English",

volume = "45",

pages = "767--775",

journal = "Nature Genetics",

issn = "1061-4036",

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Baud, A, Hermsen, R, Guryev, V, Stridh, P, Graham, D, McBride, MW, Foroud, T, Calderari, S, Diez, M, Ockinger, J, Beyeen, AD, Gillett, A, Abdelmagid, N, Guerreiro-Cacais, AO, Jagodic, M, Tuncel, J, Norin, U, Beattie, E, Huynh, N, Miller, WH, Koller, DL, Alam, I, Falak, S, Osborne-Pellegrin, M, Martinez-Membrives, E, Canete, T, Blazquez, G, Vicens-Costa, E, Mont-Cardona, C, Diaz-Moran, S, Tobena, A, Hummel, O, Zelenika, D, Saar, K, Patone, G, Bauerfeind, A, Bihoreau, MT, Heinig, M, Lee, YA, Rintisch, C, Schulz, H, Wheeler, DA, Worley, KC, Muzny, DM, Gibbs, RA, Lathrop, M, Lansu, N, Toonen, P, Ruzius, FP, De Bruijn, E, Hauser, H, Adams, DJ, Keane, T, Atanur, SS, Aitman, TJ, Flicek, P, Malinauskas, T, Jones, EY, Ekman, D, Lopez-Aumatell, R, Dominiczak, AF, Johannesson, M, Holmdahl, R, Olsson, T, Gauguier, D, Hubner, N, Fernandez-Teruel, A, Cuppen, E, Mott, R & Flint, J 2013, 'Combined sequence-based and genetic mapping analysis of complex traits in outbred rats', Nature Genetics, vol. 45, pp. 767-775. https://doi.org/10.1038/ng.2644

TY - JOUR

T1 - Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

AU - Baud, Amelie

AU - Hermsen, Roel

AU - Guryev, Victor

AU - Stridh, Pernilla

AU - Graham, Delyth

AU - McBride, Martin W.

AU - Foroud, Tatiana

AU - Calderari, Sophie

AU - Diez, Margarita

AU - Ockinger, Johan

AU - Beyeen, Amennai D.

AU - Gillett, Alan

AU - Abdelmagid, Nada

AU - Guerreiro-Cacais, Andre Ortlieb

AU - Jagodic, Maja

AU - Tuncel, Jonatan

AU - Norin, Ulrika

AU - Beattie, Elisabeth

AU - Huynh, Ngan

AU - Miller, William H.

AU - Koller, Daniel L.

AU - Alam, Imranul

AU - Falak, Samreen

AU - Osborne-Pellegrin, Mary

AU - Martinez-Membrives, Esther

AU - Canete, Toni

AU - Blazquez, Gloria

AU - Vicens-Costa, Elia

AU - Mont-Cardona, Carme

AU - Diaz-Moran, Sira

AU - Tobena, Adolf

AU - Hummel, Oliver

AU - Zelenika, Diana

AU - Saar, Kathrin

AU - Patone, Giannino

AU - Bauerfeind, Anja

AU - Bihoreau, Marie Therese

AU - Heinig, Matthias

AU - Lee, Young Ae

AU - Rintisch, Carola

AU - Schulz, Herbert

AU - Wheeler, David A.

AU - Worley, Kim C.

AU - Muzny, Donna M.

AU - Gibbs, Richard A.

AU - Lathrop, Mark

AU - Lansu, Nico

AU - Toonen, Pim

AU - Ruzius, Frans Paul

AU - De Bruijn, Ewart

AU - Hauser, Heidi

AU - Adams, David J.

AU - Keane, Thomas

AU - Atanur, Santosh S.

AU - Aitman, Tim J.

AU - Flicek, Paul

AU - Malinauskas, Tomas

AU - Jones, E. Yvonne

AU - Ekman, Diana

AU - Lopez-Aumatell, Regina

AU - Dominiczak, Anna F.

AU - Johannesson, Martina

AU - Holmdahl, Rikard

AU - Olsson, Tomas

AU - Gauguier, Dominique

AU - Hubner, Norbert

AU - Fernandez-Teruel, Alberto

AU - Cuppen, Edwin

AU - Mott, Richard

AU - Flint, Jonathan

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species. © 2013 Nature America, Inc. All rights reserved.

AB - Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species. © 2013 Nature America, Inc. All rights reserved.

U2 - https://doi.org/10.1038/ng.2644

DO - https://doi.org/10.1038/ng.2644

M3 - Article

SN - 1061-4036

VL - 45

SP - 767

EP - 775

JO - Nature Genetics

JF - Nature Genetics

ER -

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Abstract

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