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Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. / Pardiñas, Antonio F; Holmans, Peter; Pocklington, Andrew J; Escott-Price, Valentina; Ripke, Stephan; Carrera, Noa; Legge, Sophie E; Bishop, Sophie; Cameron, Darren; Hamshere, Marian L; Han, Jun; Hubbard, Leon; Lynham, Amy; Mantripragada, Kiran; Rees, Elliott; MacCabe, James H; McCarroll, Steven A; Baune, Bernhard T; Breen, Gerome; Byrne, Enda M; Dannlowski, Udo; Eley, Thalia C; Hayward, Caroline; Martin, Nicholas G; McIntosh, Andrew M; Plomin, Robert; Porteous, David J; Wray, Naomi R; Caballero, Armando; Geschwind, Daniel H; Huckins, Laura M; Ruderfer, Douglas M; Santiago, Enrique; Sklar, Pamela; Stahl, Eli A; Won, Hyejung; Agerbo, Esben; Als, Thomas D; Andreassen, Ole A; Bækvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Børglum, Anders D; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giørtz; Golimbet, Vera; Grove, Jakob; Hougaard, David M; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Søholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; GERAD1 Consortium:; CRESTAR Consortium; Collier, David A; Rujescu, Dan; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Walters, James T. R.
I:
Nature Genetics, Bind 50, 2018, s. 381-389.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
Pardiñas, AF, Holmans, P, Pocklington, AJ, Escott-Price, V, Ripke, S, Carrera, N, Legge, SE, Bishop, S, Cameron, D, Hamshere, ML, Han, J, Hubbard, L, Lynham, A, Mantripragada, K, Rees, E, MacCabe, JH, McCarroll, SA, Baune, BT, Breen, G, Byrne, EM, Dannlowski, U, Eley, TC, Hayward, C, Martin, NG, McIntosh, AM, Plomin, R, Porteous, DJ, Wray, NR, Caballero, A, Geschwind, DH, Huckins, LM, Ruderfer, DM, Santiago, E, Sklar, P, Stahl, EA, Won, H, Agerbo, E, Als, TD, Andreassen, OA, Bækvad-Hansen, M, Mortensen, PB, Pedersen, CB, Børglum, AD, Bybjerg-Grauholm, J, Djurovic, S, Durmishi, N, Pedersen, MG, Golimbet, V, Grove, J, Hougaard, DM, Mattheisen, M, Molden, E, Mors, O
, Nordentoft, M, Pejovic-Milovancevic, M, Sigurdsson, E, Silagadze, T, Hansen, CS, Stefansson, K, Stefansson, H, Steinberg, S, Tosato, S
, Werge, T, GERAD1 Consortium:, CRESTAR Consortium, Collier, DA, Rujescu, D, Kirov, G, Owen, MJ, O'Donovan, MC & Walters, JTR 2018, '
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection',
Nature Genetics, bind 50, s. 381-389.
https://doi.org/10.1038/s41588-018-0059-2APA
Pardiñas, A. F., Holmans, P., Pocklington, A. J., Escott-Price, V., Ripke, S., Carrera, N., Legge, S. E., Bishop, S., Cameron, D., Hamshere, M. L., Han, J., Hubbard, L., Lynham, A., Mantripragada, K., Rees, E., MacCabe, J. H., McCarroll, S. A., Baune, B. T., Breen, G., ... Walters, J. T. R. (2018).
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.
Nature Genetics,
50, 381-389.
https://doi.org/10.1038/s41588-018-0059-2Vancouver
Pardiñas AF, Holmans P, Pocklington AJ, Escott-Price V, Ripke S, Carrera N o.a.
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.
Nature Genetics. 2018;50:381-389.
https://doi.org/10.1038/s41588-018-0059-2Author
Pardiñas, Antonio F ; Holmans, Peter ; Pocklington, Andrew J ; Escott-Price, Valentina ; Ripke, Stephan ; Carrera, Noa ; Legge, Sophie E ; Bishop, Sophie ; Cameron, Darren ; Hamshere, Marian L ; Han, Jun ; Hubbard, Leon ; Lynham, Amy ; Mantripragada, Kiran ; Rees, Elliott ; MacCabe, James H ; McCarroll, Steven A ; Baune, Bernhard T ; Breen, Gerome ; Byrne, Enda M ; Dannlowski, Udo ; Eley, Thalia C ; Hayward, Caroline ; Martin, Nicholas G ; McIntosh, Andrew M ; Plomin, Robert ; Porteous, David J ; Wray, Naomi R ; Caballero, Armando ; Geschwind, Daniel H ; Huckins, Laura M ; Ruderfer, Douglas M ; Santiago, Enrique ; Sklar, Pamela ; Stahl, Eli A ; Won, Hyejung ; Agerbo, Esben ; Als, Thomas D ; Andreassen, Ole A ; Bækvad-Hansen, Marie ; Mortensen, Preben Bo ; Pedersen, Carsten Bøcker ; Børglum, Anders D ; Bybjerg-Grauholm, Jonas ; Djurovic, Srdjan ; Durmishi, Naser ; Pedersen, Marianne Giørtz ; Golimbet, Vera ; Grove, Jakob ; Hougaard, David M ; Mattheisen, Manuel ; Molden, Espen ; Mors, Ole ; Nordentoft, Merete ; Pejovic-Milovancevic, Milica ; Sigurdsson, Engilbert ; Silagadze, Teimuraz ; Hansen, Christine Søholm ; Stefansson, Kari ; Stefansson, Hreinn ; Steinberg, Stacy ; Tosato, Sarah ; Werge, Thomas ; GERAD1 Consortium: ; CRESTAR Consortium ; Collier, David A ; Rujescu, Dan ; Kirov, George ; Owen, Michael J ; O'Donovan, Michael C ; Walters, James T. R. / Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. I: Nature Genetics. 2018 ; Bind 50. s. 381-389.
Bibtex
@article{29b0fa3244994d9db0004ec11d1d6cb9,
title = "Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection",
abstract = "Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.",
author = "Pardi{\~n}as, {Antonio F} and Peter Holmans and Pocklington, {Andrew J} and Valentina Escott-Price and Stephan Ripke and Noa Carrera and Legge, {Sophie E} and Sophie Bishop and Darren Cameron and Hamshere, {Marian L} and Jun Han and Leon Hubbard and Amy Lynham and Kiran Mantripragada and Elliott Rees and MacCabe, {James H} and McCarroll, {Steven A} and Baune, {Bernhard T} and Gerome Breen and Byrne, {Enda M} and Udo Dannlowski and Eley, {Thalia C} and Caroline Hayward and Martin, {Nicholas G} and McIntosh, {Andrew M} and Robert Plomin and Porteous, {David J} and Wray, {Naomi R} and Armando Caballero and Geschwind, {Daniel H} and Huckins, {Laura M} and Ruderfer, {Douglas M} and Enrique Santiago and Pamela Sklar and Stahl, {Eli A} and Hyejung Won and Esben Agerbo and Als, {Thomas D} and Andreassen, {Ole A} and Marie B{\ae}kvad-Hansen and Mortensen, {Preben Bo} and Pedersen, {Carsten B{\o}cker} and B{\o}rglum, {Anders D} and Jonas Bybjerg-Grauholm and Srdjan Djurovic and Naser Durmishi and Pedersen, {Marianne Gi{\o}rtz} and Vera Golimbet and Jakob Grove and Hougaard, {David M} and Manuel Mattheisen and Espen Molden and Ole Mors and Merete Nordentoft and Milica Pejovic-Milovancevic and Engilbert Sigurdsson and Teimuraz Silagadze and Hansen, {Christine S{\o}holm} and Kari Stefansson and Hreinn Stefansson and Stacy Steinberg and Sarah Tosato and Thomas Werge and {GERAD1 Consortium:} and {CRESTAR Consortium} and Collier, {David A} and Dan Rujescu and George Kirov and Owen, {Michael J} and O'Donovan, {Michael C} and Walters, {James T. R.}",
note = "Publisher correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection (Nature Genetics, (2018), 50, 3, (381-389), DOI: 10.1038/s41588-019-0450-7",
year = "2018",
doi = "10.1038/s41588-018-0059-2",
language = "English",
volume = "50",
pages = "381--389",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
}
RIS
TY - JOUR
T1 - Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
AU - Pardiñas, Antonio F
AU - Holmans, Peter
AU - Pocklington, Andrew J
AU - Escott-Price, Valentina
AU - Ripke, Stephan
AU - Carrera, Noa
AU - Legge, Sophie E
AU - Bishop, Sophie
AU - Cameron, Darren
AU - Hamshere, Marian L
AU - Han, Jun
AU - Hubbard, Leon
AU - Lynham, Amy
AU - Mantripragada, Kiran
AU - Rees, Elliott
AU - MacCabe, James H
AU - McCarroll, Steven A
AU - Baune, Bernhard T
AU - Breen, Gerome
AU - Byrne, Enda M
AU - Dannlowski, Udo
AU - Eley, Thalia C
AU - Hayward, Caroline
AU - Martin, Nicholas G
AU - McIntosh, Andrew M
AU - Plomin, Robert
AU - Porteous, David J
AU - Wray, Naomi R
AU - Caballero, Armando
AU - Geschwind, Daniel H
AU - Huckins, Laura M
AU - Ruderfer, Douglas M
AU - Santiago, Enrique
AU - Sklar, Pamela
AU - Stahl, Eli A
AU - Won, Hyejung
AU - Agerbo, Esben
AU - Als, Thomas D
AU - Andreassen, Ole A
AU - Bækvad-Hansen, Marie
AU - Mortensen, Preben Bo
AU - Pedersen, Carsten Bøcker
AU - Børglum, Anders D
AU - Bybjerg-Grauholm, Jonas
AU - Djurovic, Srdjan
AU - Durmishi, Naser
AU - Pedersen, Marianne Giørtz
AU - Golimbet, Vera
AU - Grove, Jakob
AU - Hougaard, David M
AU - Mattheisen, Manuel
AU - Molden, Espen
AU - Mors, Ole
AU - Nordentoft, Merete
AU - Pejovic-Milovancevic, Milica
AU - Sigurdsson, Engilbert
AU - Silagadze, Teimuraz
AU - Hansen, Christine Søholm
AU - Stefansson, Kari
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Tosato, Sarah
AU - Werge, Thomas
AU - GERAD1 Consortium:
AU - CRESTAR Consortium
AU - Collier, David A
AU - Rujescu, Dan
AU - Kirov, George
AU - Owen, Michael J
AU - O'Donovan, Michael C
AU - Walters, James T. R.
N1 - Publisher correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection (Nature Genetics, (2018), 50, 3, (381-389), DOI: 10.1038/s41588-019-0450-7
PY - 2018
Y1 - 2018
N2 - Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
AB - Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
U2 - 10.1038/s41588-018-0059-2
DO - 10.1038/s41588-018-0059-2
M3 - Journal article
C2 - 29483656
VL - 50
SP - 381
EP - 389
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
