Preben Bo Mortensen

Identification of common genetic risk variants for autism spectrum disorder

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Identification of common genetic risk variants for autism spectrum disorder. / Grove, Jakob; Ripke, Stephan; Als, Thomas D; Mattheisen, Manuel; Walters, Raymond K; Won, Hyejung; Pallesen, Jonatan; Agerbo, Esben; Andreassen, Ole A; Anney, Richard; Awashti, Swapnil; Belliveau, Rich; Bettella, Francesco; Buxbaum, Joseph D; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Cerrato, Felecia; Chambert, Kimberly; Christensen, Jane H; Churchhouse, Claire; Dellenvall, Karin; Demontis, Ditte; De Rubeis, Silvia; Devlin, Bernie; Djurovic, Srdjan; Dumont, Ashley L; Goldstein, Jacqueline I; Hansen, Christine S; Hauberg, Mads Engel; Hollegaard, Mads V; Hope, Sigrun; Howrigan, Daniel P; Huang, Hailiang; Hultman, Christina M; Klei, Lambertus; Maller, Julian; Martin, Joanna; Martin, Alicia R; Moran, Jennifer L; Nyegaard, Mette; Nærland, Terje; Palmer, Duncan S; Palotie, Aarno; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; dPoterba, Timothy; Poulsen, Jesper Buchhave; Pourcain, Beate St; Qvist, Per; Rehnström, Karola ; Reichenberg, Abraham; Reichert, Jennifer ; Robinson, Elise B.; Roeder, Kathryn; Roussos, Panos; Saemundsen, Evald; Sandin, Sven; Satterstrom, F. Kyle; Smith, George Davey; Stefansson, Hreinn; Steinberg, Stacy; Stevens, Christine; Sullivan, Patrick F; Turley, Patrick; Walters, G. Bragi; Xu, Xinyi ; Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium; BUPGEN; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 23andMe Research Team; Stefansson, Kari; Geschwind, Daniel H; Nordentoft, Merete; Hougaard, David M.; Werge, Thomas; Mors, Ole; Mortensen, Preben Bo; Neale, Benjamin M; Daly, Mark J; Børglum, Anders D.

I: Nature Genetics, Bind 51, Nr. 3, 02.2019, s. 431-444.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Grove, J, Ripke, S, Als, TD, Mattheisen, M, Walters, RK, Won, H, Pallesen, J, Agerbo, E, Andreassen, OA, Anney, R, Awashti, S, Belliveau, R, Bettella, F, Buxbaum, JD, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Cerrato, F, Chambert, K, Christensen, JH, Churchhouse, C, Dellenvall, K, Demontis, D, De Rubeis, S, Devlin, B, Djurovic, S, Dumont, AL, Goldstein, JI, Hansen, CS, Hauberg, ME, Hollegaard, MV, Hope, S, Howrigan, DP, Huang, H, Hultman, CM, Klei, L, Maller, J, Martin, J, Martin, AR, Moran, JL, Nyegaard, M, Nærland, T, Palmer, DS, Palotie, A, Pedersen, CB, Pedersen, MG, dPoterba, T, Poulsen, JB, Pourcain, BS, Qvist, P, Rehnström, K, Reichenberg, A, Reichert, J, Robinson, EB, Roeder, K, Roussos, P, Saemundsen, E, Sandin, S, Satterstrom, FK, Smith, GD, Stefansson, H, Steinberg, S, Stevens, C, Sullivan, PF, Turley, P, Walters, GB, Xu, X, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Stefansson, K, Geschwind, DH, Nordentoft, M, Hougaard, DM, Werge, T, Mors, O, Mortensen, PB, Neale, BM, Daly, MJ & Børglum, AD 2019, 'Identification of common genetic risk variants for autism spectrum disorder', Nature Genetics, bind 51, nr. 3, s. 431-444. https://doi.org/10.1038/s41588-019-0344-8

APA

Grove, J., Ripke, S., Als, T. D., Mattheisen, M., Walters, R. K., Won, H., Pallesen, J., Agerbo, E., Andreassen, O. A., Anney, R., Awashti, S., Belliveau, R., Bettella, F., Buxbaum, J. D., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Cerrato, F., Chambert, K., Christensen, J. H., ... Børglum, A. D. (2019). Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51(3), 431-444. https://doi.org/10.1038/s41588-019-0344-8

CBE

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Nærland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnström K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Smith GD, Stefansson H, Steinberg S, Stevens C, Sullivan PF, Turley P, Walters GB, Xu X, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Børglum AD. 2019. Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics. 51(3):431-444. https://doi.org/10.1038/s41588-019-0344-8

MLA

Vancouver

Author

Grove, Jakob ; Ripke, Stephan ; Als, Thomas D ; Mattheisen, Manuel ; Walters, Raymond K ; Won, Hyejung ; Pallesen, Jonatan ; Agerbo, Esben ; Andreassen, Ole A ; Anney, Richard ; Awashti, Swapnil ; Belliveau, Rich ; Bettella, Francesco ; Buxbaum, Joseph D ; Bybjerg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Cerrato, Felecia ; Chambert, Kimberly ; Christensen, Jane H ; Churchhouse, Claire ; Dellenvall, Karin ; Demontis, Ditte ; De Rubeis, Silvia ; Devlin, Bernie ; Djurovic, Srdjan ; Dumont, Ashley L ; Goldstein, Jacqueline I ; Hansen, Christine S ; Hauberg, Mads Engel ; Hollegaard, Mads V ; Hope, Sigrun ; Howrigan, Daniel P ; Huang, Hailiang ; Hultman, Christina M ; Klei, Lambertus ; Maller, Julian ; Martin, Joanna ; Martin, Alicia R ; Moran, Jennifer L ; Nyegaard, Mette ; Nærland, Terje ; Palmer, Duncan S ; Palotie, Aarno ; Pedersen, Carsten Bøcker ; Pedersen, Marianne Giørtz ; dPoterba, Timothy ; Poulsen, Jesper Buchhave ; Pourcain, Beate St ; Qvist, Per ; Rehnström, Karola ; Reichenberg, Abraham ; Reichert, Jennifer ; Robinson, Elise B. ; Roeder, Kathryn ; Roussos, Panos ; Saemundsen, Evald ; Sandin, Sven ; Satterstrom, F. Kyle ; Smith, George Davey ; Stefansson, Hreinn ; Steinberg, Stacy ; Stevens, Christine ; Sullivan, Patrick F ; Turley, Patrick ; Walters, G. Bragi ; Xu, Xinyi ; Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium ; BUPGEN ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; 23andMe Research Team ; Stefansson, Kari ; Geschwind, Daniel H ; Nordentoft, Merete ; Hougaard, David M. ; Werge, Thomas ; Mors, Ole ; Mortensen, Preben Bo ; Neale, Benjamin M ; Daly, Mark J ; Børglum, Anders D. / Identification of common genetic risk variants for autism spectrum disorder. I: Nature Genetics. 2019 ; Bind 51, Nr. 3. s. 431-444.

Bibtex

@article{b950eaf23d8c43b992d4407b97360d95,
title = "Identification of common genetic risk variants for autism spectrum disorder",
abstract = "Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.",
keywords = "CELL-SURFACE, DE-NOVO, GENOME-WIDE ASSOCIATION, HERITABILITY, LD SCORE REGRESSION, LOCI, METAANALYSIS, NEURITE OUTGROWTH, SIMONS SIMPLEX COLLECTION, SYNAPTIC PLASTICITY, Humans, Child, Preschool, Genetic Predisposition to Disease/genetics, Male, Case-Control Studies, Polymorphism, Single Nucleotide/genetics, Female, Child, Autism Spectrum Disorder/genetics, Risk Factors, Multifactorial Inheritance/genetics, Phenotype, Genome-Wide Association Study/methods, Adolescent, Denmark",
author = "Jakob Grove and Stephan Ripke and Als, {Thomas D} and Manuel Mattheisen and Walters, {Raymond K} and Hyejung Won and Jonatan Pallesen and Esben Agerbo and Andreassen, {Ole A} and Richard Anney and Swapnil Awashti and Rich Belliveau and Francesco Bettella and Buxbaum, {Joseph D} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Felecia Cerrato and Kimberly Chambert and Christensen, {Jane H} and Claire Churchhouse and Karin Dellenvall and Ditte Demontis and {De Rubeis}, Silvia and Bernie Devlin and Srdjan Djurovic and Dumont, {Ashley L} and Goldstein, {Jacqueline I} and Hansen, {Christine S} and Hauberg, {Mads Engel} and Hollegaard, {Mads V} and Sigrun Hope and Howrigan, {Daniel P} and Hailiang Huang and Hultman, {Christina M} and Lambertus Klei and Julian Maller and Joanna Martin and Martin, {Alicia R} and Moran, {Jennifer L} and Mette Nyegaard and Terje N{\ae}rland and Palmer, {Duncan S} and Aarno Palotie and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Timothy dPoterba and Poulsen, {Jesper Buchhave} and Pourcain, {Beate St} and Per Qvist and Karola Rehnstr{\"o}m and Abraham Reichenberg and Jennifer Reichert and Robinson, {Elise B.} and Kathryn Roeder and Panos Roussos and Evald Saemundsen and Sven Sandin and Satterstrom, {F. Kyle} and Smith, {George Davey} and Hreinn Stefansson and Stacy Steinberg and Christine Stevens and Sullivan, {Patrick F} and Patrick Turley and Walters, {G. Bragi} and Xinyi Xu and {Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium} and BUPGEN and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and {23andMe Research Team} and Kari Stefansson and Geschwind, {Daniel H} and Merete Nordentoft and Hougaard, {David M.} and Thomas Werge and Ole Mors and Mortensen, {Preben Bo} and Neale, {Benjamin M} and Daly, {Mark J} and B{\o}rglum, {Anders D}",
year = "2019",
month = feb,
doi = "10.1038/s41588-019-0344-8",
language = "English",
volume = "51",
pages = "431--444",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

RIS

TY - JOUR

T1 - Identification of common genetic risk variants for autism spectrum disorder

AU - Grove, Jakob

AU - Ripke, Stephan

AU - Als, Thomas D

AU - Mattheisen, Manuel

AU - Walters, Raymond K

AU - Won, Hyejung

AU - Pallesen, Jonatan

AU - Agerbo, Esben

AU - Andreassen, Ole A

AU - Anney, Richard

AU - Awashti, Swapnil

AU - Belliveau, Rich

AU - Bettella, Francesco

AU - Buxbaum, Joseph D

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Cerrato, Felecia

AU - Chambert, Kimberly

AU - Christensen, Jane H

AU - Churchhouse, Claire

AU - Dellenvall, Karin

AU - Demontis, Ditte

AU - De Rubeis, Silvia

AU - Devlin, Bernie

AU - Djurovic, Srdjan

AU - Dumont, Ashley L

AU - Goldstein, Jacqueline I

AU - Hansen, Christine S

AU - Hauberg, Mads Engel

AU - Hollegaard, Mads V

AU - Hope, Sigrun

AU - Howrigan, Daniel P

AU - Huang, Hailiang

AU - Hultman, Christina M

AU - Klei, Lambertus

AU - Maller, Julian

AU - Martin, Joanna

AU - Martin, Alicia R

AU - Moran, Jennifer L

AU - Nyegaard, Mette

AU - Nærland, Terje

AU - Palmer, Duncan S

AU - Palotie, Aarno

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - dPoterba, Timothy

AU - Poulsen, Jesper Buchhave

AU - Pourcain, Beate St

AU - Qvist, Per

AU - Rehnström, Karola

AU - Reichenberg, Abraham

AU - Reichert, Jennifer

AU - Robinson, Elise B.

AU - Roeder, Kathryn

AU - Roussos, Panos

AU - Saemundsen, Evald

AU - Sandin, Sven

AU - Satterstrom, F. Kyle

AU - Smith, George Davey

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Stevens, Christine

AU - Sullivan, Patrick F

AU - Turley, Patrick

AU - Walters, G. Bragi

AU - Xu, Xinyi

AU - Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium

AU - BUPGEN

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - 23andMe Research Team

AU - Stefansson, Kari

AU - Geschwind, Daniel H

AU - Nordentoft, Merete

AU - Hougaard, David M.

AU - Werge, Thomas

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Neale, Benjamin M

AU - Daly, Mark J

AU - Børglum, Anders D

PY - 2019/2

Y1 - 2019/2

N2 - Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

AB - Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

KW - CELL-SURFACE

KW - DE-NOVO

KW - GENOME-WIDE ASSOCIATION

KW - HERITABILITY

KW - LD SCORE REGRESSION

KW - LOCI

KW - METAANALYSIS

KW - NEURITE OUTGROWTH

KW - SIMONS SIMPLEX COLLECTION

KW - SYNAPTIC PLASTICITY

KW - Humans

KW - Child, Preschool

KW - Genetic Predisposition to Disease/genetics

KW - Male

KW - Case-Control Studies

KW - Polymorphism, Single Nucleotide/genetics

KW - Female

KW - Child

KW - Autism Spectrum Disorder/genetics

KW - Risk Factors

KW - Multifactorial Inheritance/genetics

KW - Phenotype

KW - Genome-Wide Association Study/methods

KW - Adolescent

KW - Denmark

UR - http://www.scopus.com/inward/record.url?scp=85062110842&partnerID=8YFLogxK

U2 - 10.1038/s41588-019-0344-8

DO - 10.1038/s41588-019-0344-8

M3 - Journal article

C2 - 30804558

VL - 51

SP - 431

EP - 444

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -