Identification of common genetic risk variants for autism spectrum disorder

BUPGEN; 23AndMe Res Team; Psychiat Genomics Consortium; Julien Maller; Joanna Martin; Alicia Martin; J Moran; M Nyegaard; T Naerland; D Palmer; A Palotie; C Bocker Perdersen; M Giortz Pedersen; T dPoterba; J Buchhave Poulsen; B St Poucain; P Qvist; K Rehnstrom; A Reichenberg; J Reichert; E B Robinson; K Roeder; P Roussos; E Saemundsen; S Sandin; F K Satterstrom; G D Smith; H Stefansson; S Steinberg; C R  Stevens; P F  Sullivan; P Turley; G B  Walters; X Xu; K Stefansson; D H  Geschwind; M Nordentoft; D M  Hougaard; T Werge; O Mors; P B Mortensen; B M  Neale; M J  Daly; A D  Borglum

doi:10.1038/s41588-019-0344-8

Identification of common genetic risk variants for autism spectrum disorder

BUPGEN, 23AndMe Res Team, Psychiat Genomics Consortium, Julien Maller, Joanna Martin, Alicia Martin, J Moran, M Nyegaard, T Naerland, D Palmer, A Palotie, C Bocker Perdersen, M Giortz Pedersen, T dPoterba, J Buchhave Poulsen, B St Poucain, P Qvist, K Rehnstrom, A Reichenberg, J ReichertE B Robinson, K Roeder, P Roussos, E Saemundsen, S Sandin, F K Satterstrom, G D Smith, H Stefansson, S Steinberg, C R Stevens, P F Sullivan, P Turley, G B Walters, X Xu, K Stefansson, D H Geschwind, M Nordentoft, D M Hougaard, T Werge, O Mors, P B Mortensen, B M Neale, M J Daly, A D Borglum

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

Abstract / Description of output

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.

Original language	English
Pages (from-to)	431-+
Number of pages	16
Journal	Nature Genetics
Volume	51
Issue number	3
Early online date	25 Feb 2019
DOIs	https://doi.org/10.1038/s41588-019-0344-8
Publication status	Published - Mar 2019

Keywords / Materials (for Non-textual outputs)

GENOME-WIDE ASSOCIATION
SIMONS SIMPLEX COLLECTION
LD SCORE REGRESSION
DE-NOVO
SYNAPTIC PLASTICITY
NEURITE OUTGROWTH
CELL-SURFACE
LOCI
HERITABILITY
METAANALYSIS

Access to Document

10.1038/s41588-019-0344-8

GWAS_manuscript_20181009bAccepted author manuscript, 648 KB

https://research-information.bris.ac.uk/explore/en/publications/identification-of-common-genetic-risk-variants-for-autism-spectrum-disorder(91d205a6-e8f9-4e47-8058-3f8ff4029494).html

Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
UK-based charities
1/01/15 → 30/06/21
Project: Research

Cite this

BUPGEN, 23AndMe Res Team, Psychiat Genomics Consortium, Maller, J., Martin, J., Martin, A., Moran, J., Nyegaard, M., Naerland, T., Palmer, D., Palotie, A., Bocker Perdersen, C., Giortz Pedersen, M., dPoterba, T., Buchhave Poulsen, J., St Poucain, B., Qvist, P., Rehnstrom, K., Reichenberg, A., ... Borglum, A. D. (2019). Identification of common genetic risk variants for autism spectrum disorder. Nature Genetics, 51(3), 431-+. https://doi.org/10.1038/s41588-019-0344-8

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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.",

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BUPGEN, 23AndMe Res Team, Psychiat Genomics Consortium, Maller, J, Martin, J, Martin, A, Moran, J, Nyegaard, M, Naerland, T, Palmer, D, Palotie, A, Bocker Perdersen, C, Giortz Pedersen, M, dPoterba, T, Buchhave Poulsen, J, St Poucain, B, Qvist, P, Rehnstrom, K, Reichenberg, A, Reichert, J, Robinson, EB, Roeder, K, Roussos, P, Saemundsen, E, Sandin, S, Satterstrom, FK, Smith, GD, Stefansson, H, Steinberg, S, Stevens, CR, Sullivan, PF, Turley, P, Walters, GB, Xu, X, Stefansson, K, Geschwind, DH, Nordentoft, M, Hougaard, DM, Werge, T, Mors, O, Mortensen, PB, Neale, BM, Daly, MJ & Borglum, AD 2019, 'Identification of common genetic risk variants for autism spectrum disorder', Nature Genetics, vol. 51, no. 3, pp. 431-+. https://doi.org/10.1038/s41588-019-0344-8

TY - JOUR

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

AU - BUPGEN

AU - 23AndMe Res Team

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 - Baekvad-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

AU - Hansen, Christine S.

AU - Hauberg, Mads Engel

AU - Hollegaard, Mads

AU - Hope, Sigrun

AU - Howrigan, Daniel P.

AU - Huang, Hailiang

AU - Hultman, Christina M.

AU - Klei, Lambertus

AU - Psychiat Genomics Consortium

AU - Maller, Julien

AU - Martin, Joanna

AU - Martin, Alicia

AU - Moran, J

AU - Nyegaard, M

AU - Naerland, T

AU - Palmer, D

AU - Palotie, A

AU - Bocker Perdersen, C

AU - Giortz Pedersen, M

AU - dPoterba, T

AU - Buchhave Poulsen, J

AU - St Poucain, B

AU - Qvist, P

AU - Rehnstrom, K

AU - Reichenberg, A

AU - Reichert, J

AU - Robinson, E B

AU - Roeder, K

AU - Roussos, P

AU - Saemundsen, E

AU - Sandin, S

AU - Satterstrom, F K

AU - Smith, G D

AU - Stefansson, H

AU - Steinberg, S

AU - Stevens, C R

AU - Sullivan, P F

AU - Turley, P

AU - Walters, G B

AU - Xu, X

AU - Stefansson, K

AU - Geschwind, D H

AU - Nordentoft, M

AU - Hougaard, D M

AU - Werge, T

AU - Mors, O

AU - Mortensen, P B

AU - Neale, B M

AU - Daly, M J

AU - Borglum, A D

A2 - Adams, Mark J.

A2 - Blackwood, Douglas H. R.

A2 - Clarke, Toni-Kim

A2 - Davies, Gail

A2 - Deary, Ian J.

A2 - MacIntyre, Donald J.

A2 - Thomson, Pippa A.

A2 - Hayward, Caroline

A2 - McIntosh, Andrew M.

A2 - Porteous, David J.

PY - 2019/3

Y1 - 2019/3

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 - GENOME-WIDE ASSOCIATION

KW - SIMONS SIMPLEX COLLECTION

KW - LD SCORE REGRESSION

KW - DE-NOVO

KW - SYNAPTIC PLASTICITY

KW - NEURITE OUTGROWTH

KW - CELL-SURFACE

KW - LOCI

KW - HERITABILITY

KW - METAANALYSIS

U2 - 10.1038/s41588-019-0344-8

DO - 10.1038/s41588-019-0344-8

M3 - Article

SN - 1061-4036

VL - 51

SP - 431-+

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Identification of common genetic risk variants for autism spectrum disorder

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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Stratifying Resilience and Depression Longitudinally

Cite this