PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

Catherine Sudlow; Marina  Mola-Caminal; Caty  Carrera; Carolina  Soriano-Tárraga; Eva Giralt-Steinhauer; Rosa  M. Díaz-Navarro; Sílvia  Tur; Carmen  Jiménez4; Aina  Medina-Dols; Natàlia  Cullell; Nuria Pazos; Torres Aguila; Elena  Muiño; Ana  Rodríguez-Campello; Angel  Ois; Elisa Cuadrado-godia; Rosa M Vivanco-Hidalgo; Mar  Hernandez-Guillamon; Montse Solé; Pilar Delgado; Alejandro Bustamante; Teresa García-Berrocoso; Maite  Mendióroz; Mar Castellanos; Joaquín  Serena; Joan  Martí-Fàbregas; Tomás  Segura; Gemma  Serrano-Heras; Victor  Obach; Marc  Ribó; Carlos A  Molina; José Álvarez Sabín; Ernest  Palomeras; Mar  Freijo; Maria A Font; Jonathan Rosand; Natalia S Rost; Cristina  Gallego-Fabrega; Jin-Moo Lee; Laura Heitsch; Laura  Ibanez; Carlos Cruchaga; Chia-ling Phuah; Robin Lemmens; Vincent Thijs; Arne Lindgren; Jane  Maguire; Kristiina Rannikmae; Christina Jern; Tara M Stanne; Erik Lorentzen; Lucía  Muñoz-Narbona; Antonio Davalos; Elena  López-Cancio; Bradford B Worrall; Daniel Woo; Steven J Kittner; Braxton D. Mitchell; Joan Montaner; Jaume Roquer; Jurek  Krupinski; Xavier Estivill; Raquel Rabionet; Cristòfol  Vives-Bauzá; Israel Fernandez-Cadenas; Jordi Jiménez-Conde

doi:10.1161/CIRCRESAHA.118.313533

PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

Catherine Sudlow, Marina Mola-Caminal, Caty Carrera, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Rosa M. Díaz-Navarro, Sílvia Tur, Carmen Jiménez4, Aina Medina-Dols, Natàlia Cullell, Nuria Pazos, Torres Aguila, Elena Muiño, Ana Rodríguez-Campello, Angel Ois, Elisa Cuadrado-godia, Rosa M Vivanco-Hidalgo, Mar Hernandez-Guillamon, Montse Solé, Pilar DelgadoAlejandro Bustamante, Teresa García-Berrocoso, Maite Mendióroz, Mar Castellanos, Joaquín Serena, Joan Martí-Fàbregas, Tomás Segura, Gemma Serrano-Heras, Victor Obach, Marc Ribó, Carlos A Molina , José Álvarez Sabín, Ernest Palomeras, Mar Freijo , Maria A Font, Jonathan Rosand, Natalia S Rost, Cristina Gallego-Fabrega, Jin-Moo Lee, Laura Heitsch, Laura Ibanez, Carlos Cruchaga, Chia-ling Phuah, Robin Lemmens, Vincent Thijs, Arne Lindgren, Jane Maguire, Kristiina Rannikmae, Christina Jern, Tara M Stanne, Erik Lorentzen, Lucía Muñoz-Narbona, Antonio Davalos, Elena López-Cancio, Bradford B Worrall, Daniel Woo, Steven J Kittner, Braxton D. Mitchell, Joan Montaner, Jaume Roquer, Jurek Krupinski, Xavier Estivill, Raquel Rabionet, Cristòfol Vives-Bauzá, Israel Fernandez-Cadenas, Jordi Jiménez-Conde

Research output: Contribution to journal › Article › peer-review

Abstract

RATIONALE: Ischemic stroke (IS) is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome.

OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date.

METHODS AND RESULTS: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9).

CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.

Original language	English
Pages (from-to)	114-120
Number of pages	7
Journal	Circulation Research
Volume	124
Issue number	1
Early online date	15 Oct 2018
DOIs	https://doi.org/10.1161/CIRCRESAHA.118.313533
Publication status	Published - Jan 2019

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10.1161/CIRCRESAHA.118.313533

PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome A Genome-Wide Meta-Analysis
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Sudlow, C., Mola-Caminal, M., Carrera, C., Soriano-Tárraga, C., Giralt-Steinhauer, E., M. Díaz-Navarro, R., Tur, S., Jiménez4, C., Medina-Dols, A., Cullell, N., Pazos, N., Aguila, T., Muiño, E., Rodríguez-Campello, A., Ois, A., Cuadrado-godia, E., Vivanco-Hidalgo, R. M., Hernandez-Guillamon, M., Solé, M., ... Jiménez-Conde, J. (2019). PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis. Circulation Research, 124(1), 114-120. https://doi.org/10.1161/CIRCRESAHA.118.313533

@article{53445588520b4a9a84f505a7e3d9606e,

title = "PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis",

abstract = "RATIONALE: Ischemic stroke (IS) is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date. METHODS AND RESULTS: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.",

author = "Catherine Sudlow and Marina Mola-Caminal and Caty Carrera and Carolina Soriano-T{\'a}rraga and Eva Giralt-Steinhauer and \{M. D{\'i}az-Navarro\}, Rosa and S{\'i}lvia Tur and Carmen Jim{\'e}nez4 and Aina Medina-Dols and Nat{\`a}lia Cullell and Nuria Pazos and Torres Aguila and Elena Mui{\~n}o and Ana Rodr{\'i}guez-Campello and Angel Ois and Elisa Cuadrado-godia and Vivanco-Hidalgo, \{Rosa M\} and Mar Hernandez-Guillamon and Montse Sol{\'e} and Pilar Delgado and Alejandro Bustamante and Teresa Garc{\'i}a-Berrocoso and Maite Mendi{\'o}roz and Mar Castellanos and Joaqu{\'i}n Serena and Joan Mart{\'i}-F{\`a}bregas and Tom{\'a}s Segura and Gemma Serrano-Heras and Victor Obach and Marc Rib{\'o} and Molina, \{Carlos A\} and Sab{\'i}n, \{Jos{\'e} {\'A}lvarez\} and Ernest Palomeras and Mar Freijo and Font, \{Maria A\} and Jonathan Rosand and Rost, \{Natalia S\} and Cristina Gallego-Fabrega and Jin-Moo Lee and Laura Heitsch and Laura Ibanez and Carlos Cruchaga and Chia-ling Phuah and Robin Lemmens and Vincent Thijs and Arne Lindgren and Jane Maguire and Kristiina Rannikmae and Christina Jern and Stanne, \{Tara M\} and Erik Lorentzen and Luc{\'i}a Mu{\~n}oz-Narbona and Antonio Davalos and Elena L{\'o}pez-Cancio and Worrall, \{Bradford B\} and Daniel Woo and Kittner, \{Steven J\} and Mitchell, \{Braxton D.\} and Joan Montaner and Jaume Roquer and Jurek Krupinski and Xavier Estivill and Raquel Rabionet and Crist{\`o}fol Vives-Bauz{\'a} and Israel Fernandez-Cadenas and Jordi Jim{\'e}nez-Conde",

year = "2019",

month = jan,

doi = "10.1161/CIRCRESAHA.118.313533",

language = "English",

volume = "124",

pages = "114--120",

journal = "Circulation Research",

issn = "0009-7330",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

Sudlow, C, Mola-Caminal, M, Carrera, C, Soriano-Tárraga, C, Giralt-Steinhauer, E, M. Díaz-Navarro, R, Tur, S, Jiménez4, C, Medina-Dols, A, Cullell, N, Pazos, N, Aguila, T, Muiño, E, Rodríguez-Campello, A, Ois, A, Cuadrado-godia, E, Vivanco-Hidalgo, RM, Hernandez-Guillamon, M, Solé, M, Delgado, P, Bustamante, A, García-Berrocoso, T, Mendióroz, M, Castellanos, M, Serena, J, Martí-Fàbregas, J, Segura, T, Serrano-Heras, G, Obach, V, Ribó, M, Molina , CA, Sabín, JÁ, Palomeras, E, Freijo , M, Font, MA, Rosand, J, Rost, NS, Gallego-Fabrega, C, Lee, J-M, Heitsch, L, Ibanez, L, Cruchaga, C, Phuah, C, Lemmens, R, Thijs, V, Lindgren, A, Maguire, J, Rannikmae, K, Jern, C, Stanne, TM, Lorentzen, E, Muñoz-Narbona, L, Davalos, A, López-Cancio, E, Worrall, BB, Woo, D, Kittner, SJ, Mitchell, BD, Montaner, J, Roquer, J, Krupinski, J, Estivill, X, Rabionet, R, Vives-Bauzá, C, Fernandez-Cadenas, I & Jiménez-Conde, J 2019, 'PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis', Circulation Research, vol. 124, no. 1, pp. 114-120. https://doi.org/10.1161/CIRCRESAHA.118.313533

TY - JOUR

T1 - PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

AU - Sudlow, Catherine

AU - Mola-Caminal, Marina

AU - Carrera, Caty

AU - Soriano-Tárraga, Carolina

AU - Giralt-Steinhauer, Eva

AU - M. Díaz-Navarro, Rosa

AU - Tur, Sílvia

AU - Jiménez4, Carmen

AU - Medina-Dols, Aina

AU - Cullell, Natàlia

AU - Pazos, Nuria

AU - Aguila, Torres

AU - Muiño, Elena

AU - Rodríguez-Campello, Ana

AU - Ois, Angel

AU - Cuadrado-godia, Elisa

AU - Vivanco-Hidalgo, Rosa M

AU - Hernandez-Guillamon, Mar

AU - Solé, Montse

AU - Delgado, Pilar

AU - Bustamante, Alejandro

AU - García-Berrocoso, Teresa

AU - Mendióroz, Maite

AU - Castellanos, Mar

AU - Serena, Joaquín

AU - Martí-Fàbregas, Joan

AU - Segura, Tomás

AU - Serrano-Heras, Gemma

AU - Obach, Victor

AU - Ribó, Marc

AU - Molina , Carlos A

AU - Sabín, José Álvarez

AU - Palomeras, Ernest

AU - Freijo , Mar

AU - Font, Maria A

AU - Rosand, Jonathan

AU - Rost, Natalia S

AU - Gallego-Fabrega, Cristina

AU - Lee, Jin-Moo

AU - Heitsch, Laura

AU - Ibanez, Laura

AU - Cruchaga, Carlos

AU - Phuah, Chia-ling

AU - Lemmens, Robin

AU - Thijs, Vincent

AU - Lindgren, Arne

AU - Maguire, Jane

AU - Rannikmae, Kristiina

AU - Jern, Christina

AU - Stanne, Tara M

AU - Lorentzen, Erik

AU - Muñoz-Narbona, Lucía

AU - Davalos, Antonio

AU - López-Cancio, Elena

AU - Worrall, Bradford B

AU - Woo, Daniel

AU - Kittner, Steven J

AU - Mitchell, Braxton D.

AU - Montaner, Joan

AU - Roquer, Jaume

AU - Krupinski, Jurek

AU - Estivill, Xavier

AU - Rabionet, Raquel

AU - Vives-Bauzá, Cristòfol

AU - Fernandez-Cadenas, Israel

AU - Jiménez-Conde, Jordi

PY - 2019/1

Y1 - 2019/1

N2 - RATIONALE: Ischemic stroke (IS) is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date. METHODS AND RESULTS: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.

AB - RATIONALE: Ischemic stroke (IS) is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date. METHODS AND RESULTS: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.

U2 - 10.1161/CIRCRESAHA.118.313533

DO - 10.1161/CIRCRESAHA.118.313533

M3 - Article

C2 - 30582445

SN - 0009-7330

VL - 124

SP - 114

EP - 120

JO - Circulation Research

JF - Circulation Research

IS - 1

ER -

PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

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