The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders
Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this chall...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Eva Loth [verfasserIn] Tony Charman [verfasserIn] Luke Mason [verfasserIn] Julian Tillmann [verfasserIn] Emily J. H. Jones [verfasserIn] Caroline Wooldridge [verfasserIn] Jumana Ahmad [verfasserIn] Bonnie Auyeung [verfasserIn] Claudia Brogna [verfasserIn] Sara Ambrosino [verfasserIn] Tobias Banaschewski [verfasserIn] Simon Baron-Cohen [verfasserIn] Sarah Baumeister [verfasserIn] Christian Beckmann [verfasserIn] Michael Brammer [verfasserIn] Daniel Brandeis [verfasserIn] Sven Bölte [verfasserIn] Thomas Bourgeron [verfasserIn] Carsten Bours [verfasserIn] Yvette de Bruijn [verfasserIn] Bhismadev Chakrabarti [verfasserIn] Daisy Crawley [verfasserIn] Ineke Cornelissen [verfasserIn] Flavio Dell’ Acqua [verfasserIn] Guillaume Dumas [verfasserIn] Sarah Durston [verfasserIn] Christine Ecker [verfasserIn] Jessica Faulkner [verfasserIn] Vincent Frouin [verfasserIn] Pilar Garces [verfasserIn] David Goyard [verfasserIn] Hannah Hayward [verfasserIn] Lindsay M. Ham [verfasserIn] Joerg Hipp [verfasserIn] Rosemary J. Holt [verfasserIn] Mark H. Johnson [verfasserIn] Johan Isaksson [verfasserIn] Prantik Kundu [verfasserIn] Meng-Chuan Lai [verfasserIn] Xavier Liogier D’ardhuy [verfasserIn] Michael V. Lombardo [verfasserIn] David J. Lythgoe [verfasserIn] René Mandl [verfasserIn] Andreas Meyer-Lindenberg [verfasserIn] Carolin Moessnang [verfasserIn] Nico Mueller [verfasserIn] Laurence O’Dwyer [verfasserIn] Marianne Oldehinkel [verfasserIn] Bob Oranje [verfasserIn] Gahan Pandina [verfasserIn] Antonio M. Persico [verfasserIn] Amber N. V. Ruigrok [verfasserIn] Barbara Ruggeri [verfasserIn] Jessica Sabet [verfasserIn] Roberto Sacco [verfasserIn] Antonia San José Cáceres [verfasserIn] Emily Simonoff [verfasserIn] Roberto Toro [verfasserIn] Heike Tost [verfasserIn] Jack Waldman [verfasserIn] Steve C. R. Williams [verfasserIn] Marcel P. Zwiers [verfasserIn] Will Spooren [verfasserIn] Declan G. M. Murphy [verfasserIn] Jan K. Buitelaar [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Molecular Autism - BMC, 2010, 8(2017), 1, Seite 19 |
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| Übergeordnetes Werk: |
volume:8 ; year:2017 ; number:1 ; pages:19 |
| Links: |
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| DOI / URN: |
10.1186/s13229-017-0146-8 |
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DOAJ073958506 |
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| 245 | 1 | 4 | |a The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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| 520 | |a Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. | ||
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10.1186/s13229-017-0146-8 doi (DE-627)DOAJ073958506 (DE-599)DOAJ861e74108f4d4b93970934cad6c3418b DE-627 ger DE-627 rakwb eng RC346-429 Eva Loth verfasserin aut The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking Neurology. Diseases of the nervous system Tony Charman verfasserin aut Luke Mason verfasserin aut Julian Tillmann verfasserin aut Emily J. H. Jones verfasserin aut Caroline Wooldridge verfasserin aut Jumana Ahmad verfasserin aut Bonnie Auyeung verfasserin aut Claudia Brogna verfasserin aut Sara Ambrosino verfasserin aut Tobias Banaschewski verfasserin aut Simon Baron-Cohen verfasserin aut Sarah Baumeister verfasserin aut Christian Beckmann verfasserin aut Michael Brammer verfasserin aut Daniel Brandeis verfasserin aut Sven Bölte verfasserin aut Thomas Bourgeron verfasserin aut Carsten Bours verfasserin aut Yvette de Bruijn verfasserin aut Bhismadev Chakrabarti verfasserin aut Daisy Crawley verfasserin aut Ineke Cornelissen verfasserin aut Flavio Dell’ Acqua verfasserin aut Guillaume Dumas verfasserin aut Sarah Durston verfasserin aut Christine Ecker verfasserin aut Jessica Faulkner verfasserin aut Vincent Frouin verfasserin aut Pilar Garces verfasserin aut David Goyard verfasserin aut Hannah Hayward verfasserin aut Lindsay M. Ham verfasserin aut Joerg Hipp verfasserin aut Rosemary J. Holt verfasserin aut Mark H. 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10.1186/s13229-017-0146-8 doi (DE-627)DOAJ073958506 (DE-599)DOAJ861e74108f4d4b93970934cad6c3418b DE-627 ger DE-627 rakwb eng RC346-429 Eva Loth verfasserin aut The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking Neurology. Diseases of the nervous system Tony Charman verfasserin aut Luke Mason verfasserin aut Julian Tillmann verfasserin aut Emily J. H. Jones verfasserin aut Caroline Wooldridge verfasserin aut Jumana Ahmad verfasserin aut Bonnie Auyeung verfasserin aut Claudia Brogna verfasserin aut Sara Ambrosino verfasserin aut Tobias Banaschewski verfasserin aut Simon Baron-Cohen verfasserin aut Sarah Baumeister verfasserin aut Christian Beckmann verfasserin aut Michael Brammer verfasserin aut Daniel Brandeis verfasserin aut Sven Bölte verfasserin aut Thomas Bourgeron verfasserin aut Carsten Bours verfasserin aut Yvette de Bruijn verfasserin aut Bhismadev Chakrabarti verfasserin aut Daisy Crawley verfasserin aut Ineke Cornelissen verfasserin aut Flavio Dell’ Acqua verfasserin aut Guillaume Dumas verfasserin aut Sarah Durston verfasserin aut Christine Ecker verfasserin aut Jessica Faulkner verfasserin aut Vincent Frouin verfasserin aut Pilar Garces verfasserin aut David Goyard verfasserin aut Hannah Hayward verfasserin aut Lindsay M. Ham verfasserin aut Joerg Hipp verfasserin aut Rosemary J. Holt verfasserin aut Mark H. Johnson verfasserin aut Johan Isaksson verfasserin aut Prantik Kundu verfasserin aut Meng-Chuan Lai verfasserin aut Xavier Liogier D’ardhuy verfasserin aut Michael V. Lombardo verfasserin aut David J. Lythgoe verfasserin aut René Mandl verfasserin aut Andreas Meyer-Lindenberg verfasserin aut Carolin Moessnang verfasserin aut Nico Mueller verfasserin aut Laurence O’Dwyer verfasserin aut Marianne Oldehinkel verfasserin aut Bob Oranje verfasserin aut Gahan Pandina verfasserin aut Antonio M. Persico verfasserin aut Amber N. V. Ruigrok verfasserin aut Barbara Ruggeri verfasserin aut Jessica Sabet verfasserin aut Roberto Sacco verfasserin aut Antonia San José Cáceres verfasserin aut Emily Simonoff verfasserin aut Roberto Toro verfasserin aut Heike Tost verfasserin aut Jack Waldman verfasserin aut Steve C. R. Williams verfasserin aut Marcel P. Zwiers verfasserin aut Will Spooren verfasserin aut Declan G. M. Murphy verfasserin aut Jan K. Buitelaar verfasserin aut In Molecular Autism BMC, 2010 8(2017), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:8 year:2017 number:1 pages:19 https://doi.org/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/article/861e74108f4d4b93970934cad6c3418b kostenfrei http://link.springer.com/article/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 1 19 |
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10.1186/s13229-017-0146-8 doi (DE-627)DOAJ073958506 (DE-599)DOAJ861e74108f4d4b93970934cad6c3418b DE-627 ger DE-627 rakwb eng RC346-429 Eva Loth verfasserin aut The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking Neurology. Diseases of the nervous system Tony Charman verfasserin aut Luke Mason verfasserin aut Julian Tillmann verfasserin aut Emily J. H. Jones verfasserin aut Caroline Wooldridge verfasserin aut Jumana Ahmad verfasserin aut Bonnie Auyeung verfasserin aut Claudia Brogna verfasserin aut Sara Ambrosino verfasserin aut Tobias Banaschewski verfasserin aut Simon Baron-Cohen verfasserin aut Sarah Baumeister verfasserin aut Christian Beckmann verfasserin aut Michael Brammer verfasserin aut Daniel Brandeis verfasserin aut Sven Bölte verfasserin aut Thomas Bourgeron verfasserin aut Carsten Bours verfasserin aut Yvette de Bruijn verfasserin aut Bhismadev Chakrabarti verfasserin aut Daisy Crawley verfasserin aut Ineke Cornelissen verfasserin aut Flavio Dell’ Acqua verfasserin aut Guillaume Dumas verfasserin aut Sarah Durston verfasserin aut Christine Ecker verfasserin aut Jessica Faulkner verfasserin aut Vincent Frouin verfasserin aut Pilar Garces verfasserin aut David Goyard verfasserin aut Hannah Hayward verfasserin aut Lindsay M. Ham verfasserin aut Joerg Hipp verfasserin aut Rosemary J. Holt verfasserin aut Mark H. Johnson verfasserin aut Johan Isaksson verfasserin aut Prantik Kundu verfasserin aut Meng-Chuan Lai verfasserin aut Xavier Liogier D’ardhuy verfasserin aut Michael V. Lombardo verfasserin aut David J. Lythgoe verfasserin aut René Mandl verfasserin aut Andreas Meyer-Lindenberg verfasserin aut Carolin Moessnang verfasserin aut Nico Mueller verfasserin aut Laurence O’Dwyer verfasserin aut Marianne Oldehinkel verfasserin aut Bob Oranje verfasserin aut Gahan Pandina verfasserin aut Antonio M. Persico verfasserin aut Amber N. V. Ruigrok verfasserin aut Barbara Ruggeri verfasserin aut Jessica Sabet verfasserin aut Roberto Sacco verfasserin aut Antonia San José Cáceres verfasserin aut Emily Simonoff verfasserin aut Roberto Toro verfasserin aut Heike Tost verfasserin aut Jack Waldman verfasserin aut Steve C. R. Williams verfasserin aut Marcel P. Zwiers verfasserin aut Will Spooren verfasserin aut Declan G. M. Murphy verfasserin aut Jan K. Buitelaar verfasserin aut In Molecular Autism BMC, 2010 8(2017), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:8 year:2017 number:1 pages:19 https://doi.org/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/article/861e74108f4d4b93970934cad6c3418b kostenfrei http://link.springer.com/article/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 1 19 |
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10.1186/s13229-017-0146-8 doi (DE-627)DOAJ073958506 (DE-599)DOAJ861e74108f4d4b93970934cad6c3418b DE-627 ger DE-627 rakwb eng RC346-429 Eva Loth verfasserin aut The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking Neurology. Diseases of the nervous system Tony Charman verfasserin aut Luke Mason verfasserin aut Julian Tillmann verfasserin aut Emily J. H. Jones verfasserin aut Caroline Wooldridge verfasserin aut Jumana Ahmad verfasserin aut Bonnie Auyeung verfasserin aut Claudia Brogna verfasserin aut Sara Ambrosino verfasserin aut Tobias Banaschewski verfasserin aut Simon Baron-Cohen verfasserin aut Sarah Baumeister verfasserin aut Christian Beckmann verfasserin aut Michael Brammer verfasserin aut Daniel Brandeis verfasserin aut Sven Bölte verfasserin aut Thomas Bourgeron verfasserin aut Carsten Bours verfasserin aut Yvette de Bruijn verfasserin aut Bhismadev Chakrabarti verfasserin aut Daisy Crawley verfasserin aut Ineke Cornelissen verfasserin aut Flavio Dell’ Acqua verfasserin aut Guillaume Dumas verfasserin aut Sarah Durston verfasserin aut Christine Ecker verfasserin aut Jessica Faulkner verfasserin aut Vincent Frouin verfasserin aut Pilar Garces verfasserin aut David Goyard verfasserin aut Hannah Hayward verfasserin aut Lindsay M. Ham verfasserin aut Joerg Hipp verfasserin aut Rosemary J. Holt verfasserin aut Mark H. Johnson verfasserin aut Johan Isaksson verfasserin aut Prantik Kundu verfasserin aut Meng-Chuan Lai verfasserin aut Xavier Liogier D’ardhuy verfasserin aut Michael V. Lombardo verfasserin aut David J. Lythgoe verfasserin aut René Mandl verfasserin aut Andreas Meyer-Lindenberg verfasserin aut Carolin Moessnang verfasserin aut Nico Mueller verfasserin aut Laurence O’Dwyer verfasserin aut Marianne Oldehinkel verfasserin aut Bob Oranje verfasserin aut Gahan Pandina verfasserin aut Antonio M. Persico verfasserin aut Amber N. V. Ruigrok verfasserin aut Barbara Ruggeri verfasserin aut Jessica Sabet verfasserin aut Roberto Sacco verfasserin aut Antonia San José Cáceres verfasserin aut Emily Simonoff verfasserin aut Roberto Toro verfasserin aut Heike Tost verfasserin aut Jack Waldman verfasserin aut Steve C. R. Williams verfasserin aut Marcel P. Zwiers verfasserin aut Will Spooren verfasserin aut Declan G. M. Murphy verfasserin aut Jan K. Buitelaar verfasserin aut In Molecular Autism BMC, 2010 8(2017), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:8 year:2017 number:1 pages:19 https://doi.org/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/article/861e74108f4d4b93970934cad6c3418b kostenfrei http://link.springer.com/article/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 1 19 |
| allfieldsSound |
10.1186/s13229-017-0146-8 doi (DE-627)DOAJ073958506 (DE-599)DOAJ861e74108f4d4b93970934cad6c3418b DE-627 ger DE-627 rakwb eng RC346-429 Eva Loth verfasserin aut The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking Neurology. Diseases of the nervous system Tony Charman verfasserin aut Luke Mason verfasserin aut Julian Tillmann verfasserin aut Emily J. H. Jones verfasserin aut Caroline Wooldridge verfasserin aut Jumana Ahmad verfasserin aut Bonnie Auyeung verfasserin aut Claudia Brogna verfasserin aut Sara Ambrosino verfasserin aut Tobias Banaschewski verfasserin aut Simon Baron-Cohen verfasserin aut Sarah Baumeister verfasserin aut Christian Beckmann verfasserin aut Michael Brammer verfasserin aut Daniel Brandeis verfasserin aut Sven Bölte verfasserin aut Thomas Bourgeron verfasserin aut Carsten Bours verfasserin aut Yvette de Bruijn verfasserin aut Bhismadev Chakrabarti verfasserin aut Daisy Crawley verfasserin aut Ineke Cornelissen verfasserin aut Flavio Dell’ Acqua verfasserin aut Guillaume Dumas verfasserin aut Sarah Durston verfasserin aut Christine Ecker verfasserin aut Jessica Faulkner verfasserin aut Vincent Frouin verfasserin aut Pilar Garces verfasserin aut David Goyard verfasserin aut Hannah Hayward verfasserin aut Lindsay M. Ham verfasserin aut Joerg Hipp verfasserin aut Rosemary J. Holt verfasserin aut Mark H. Johnson verfasserin aut Johan Isaksson verfasserin aut Prantik Kundu verfasserin aut Meng-Chuan Lai verfasserin aut Xavier Liogier D’ardhuy verfasserin aut Michael V. Lombardo verfasserin aut David J. Lythgoe verfasserin aut René Mandl verfasserin aut Andreas Meyer-Lindenberg verfasserin aut Carolin Moessnang verfasserin aut Nico Mueller verfasserin aut Laurence O’Dwyer verfasserin aut Marianne Oldehinkel verfasserin aut Bob Oranje verfasserin aut Gahan Pandina verfasserin aut Antonio M. Persico verfasserin aut Amber N. V. Ruigrok verfasserin aut Barbara Ruggeri verfasserin aut Jessica Sabet verfasserin aut Roberto Sacco verfasserin aut Antonia San José Cáceres verfasserin aut Emily Simonoff verfasserin aut Roberto Toro verfasserin aut Heike Tost verfasserin aut Jack Waldman verfasserin aut Steve C. R. Williams verfasserin aut Marcel P. Zwiers verfasserin aut Will Spooren verfasserin aut Declan G. M. Murphy verfasserin aut Jan K. Buitelaar verfasserin aut In Molecular Autism BMC, 2010 8(2017), 1, Seite 19 (DE-627)620141522 (DE-600)2540930-X 20402392 nnns volume:8 year:2017 number:1 pages:19 https://doi.org/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/article/861e74108f4d4b93970934cad6c3418b kostenfrei http://link.springer.com/article/10.1186/s13229-017-0146-8 kostenfrei https://doaj.org/toc/2040-2392 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017 1 19 |
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Eva Loth @@aut@@ Tony Charman @@aut@@ Luke Mason @@aut@@ Julian Tillmann @@aut@@ Emily J. H. Jones @@aut@@ Caroline Wooldridge @@aut@@ Jumana Ahmad @@aut@@ Bonnie Auyeung @@aut@@ Claudia Brogna @@aut@@ Sara Ambrosino @@aut@@ Tobias Banaschewski @@aut@@ Simon Baron-Cohen @@aut@@ Sarah Baumeister @@aut@@ Christian Beckmann @@aut@@ Michael Brammer @@aut@@ Daniel Brandeis @@aut@@ Sven Bölte @@aut@@ Thomas Bourgeron @@aut@@ Carsten Bours @@aut@@ Yvette de Bruijn @@aut@@ Bhismadev Chakrabarti @@aut@@ Daisy Crawley @@aut@@ Ineke Cornelissen @@aut@@ Flavio Dell’ Acqua @@aut@@ Guillaume Dumas @@aut@@ Sarah Durston @@aut@@ Christine Ecker @@aut@@ Jessica Faulkner @@aut@@ Vincent Frouin @@aut@@ Pilar Garces @@aut@@ David Goyard @@aut@@ Hannah Hayward @@aut@@ Lindsay M. Ham @@aut@@ Joerg Hipp @@aut@@ Rosemary J. Holt @@aut@@ Mark H. Johnson @@aut@@ Johan Isaksson @@aut@@ Prantik Kundu @@aut@@ Meng-Chuan Lai @@aut@@ Xavier Liogier D’ardhuy @@aut@@ Michael V. Lombardo @@aut@@ David J. Lythgoe @@aut@@ René Mandl @@aut@@ Andreas Meyer-Lindenberg @@aut@@ Carolin Moessnang @@aut@@ Nico Mueller @@aut@@ Laurence O’Dwyer @@aut@@ Marianne Oldehinkel @@aut@@ Bob Oranje @@aut@@ Gahan Pandina @@aut@@ Antonio M. Persico @@aut@@ Amber N. V. Ruigrok @@aut@@ Barbara Ruggeri @@aut@@ Jessica Sabet @@aut@@ Roberto Sacco @@aut@@ Antonia San José Cáceres @@aut@@ Emily Simonoff @@aut@@ Roberto Toro @@aut@@ Heike Tost @@aut@@ Jack Waldman @@aut@@ Steve C. R. Williams @@aut@@ Marcel P. Zwiers @@aut@@ Will Spooren @@aut@@ Declan G. M. Murphy @@aut@@ Jan K. Buitelaar @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ073958506</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309121857.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2017 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13229-017-0146-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ073958506</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ861e74108f4d4b93970934cad6c3418b</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC346-429</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Eva Loth</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Biomarkers</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cognition</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Neuroimaging</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">MRI</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">EEG</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Eye-tracking</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neurology. 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R - Medicine |
| author |
Eva Loth |
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Eva Loth misc RC346-429 misc Biomarkers misc Cognition misc Neuroimaging misc MRI misc EEG misc Eye-tracking misc Neurology. Diseases of the nervous system The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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Eva Loth |
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aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
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20402392 |
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RC346-429 The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders Biomarkers Cognition Neuroimaging MRI EEG Eye-tracking |
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misc RC346-429 misc Biomarkers misc Cognition misc Neuroimaging misc MRI misc EEG misc Eye-tracking misc Neurology. Diseases of the nervous system |
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misc RC346-429 misc Biomarkers misc Cognition misc Neuroimaging misc MRI misc EEG misc Eye-tracking misc Neurology. Diseases of the nervous system |
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The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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Eva Loth |
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Molecular Autism |
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Eva Loth Tony Charman Luke Mason Julian Tillmann Emily J. H. Jones Caroline Wooldridge Jumana Ahmad Bonnie Auyeung Claudia Brogna Sara Ambrosino Tobias Banaschewski Simon Baron-Cohen Sarah Baumeister Christian Beckmann Michael Brammer Daniel Brandeis Sven Bölte Thomas Bourgeron Carsten Bours Yvette de Bruijn Bhismadev Chakrabarti Daisy Crawley Ineke Cornelissen Flavio Dell’ Acqua Guillaume Dumas Sarah Durston Christine Ecker Jessica Faulkner Vincent Frouin Pilar Garces David Goyard Hannah Hayward Lindsay M. Ham Joerg Hipp Rosemary J. Holt Mark H. Johnson Johan Isaksson Prantik Kundu Meng-Chuan Lai Xavier Liogier D’ardhuy Michael V. Lombardo David J. Lythgoe René Mandl Andreas Meyer-Lindenberg Carolin Moessnang Nico Mueller Laurence O’Dwyer Marianne Oldehinkel Bob Oranje Gahan Pandina Antonio M. Persico Amber N. V. Ruigrok Barbara Ruggeri Jessica Sabet Roberto Sacco Antonia San José Cáceres Emily Simonoff Roberto Toro Heike Tost Jack Waldman Steve C. R. Williams Marcel P. Zwiers Will Spooren Declan G. M. Murphy Jan K. Buitelaar |
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eu-aims longitudinal european autism project (leap): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. |
| abstractGer |
Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. |
| abstract_unstemmed |
Abstract Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. |
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The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders |
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https://doi.org/10.1186/s13229-017-0146-8 https://doaj.org/article/861e74108f4d4b93970934cad6c3418b http://link.springer.com/article/10.1186/s13229-017-0146-8 https://doaj.org/toc/2040-2392 |
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Tony Charman Luke Mason Julian Tillmann Emily J. H. Jones Caroline Wooldridge Jumana Ahmad Bonnie Auyeung Claudia Brogna Sara Ambrosino Tobias Banaschewski Simon Baron-Cohen Sarah Baumeister Christian Beckmann Michael Brammer Daniel Brandeis Sven Bölte Thomas Bourgeron Carsten Bours Yvette de Bruijn Bhismadev Chakrabarti Daisy Crawley Ineke Cornelissen Flavio Dell’ Acqua Guillaume Dumas Sarah Durston Christine Ecker Jessica Faulkner Vincent Frouin Pilar Garces David Goyard Hannah Hayward Lindsay M. Ham Joerg Hipp Rosemary J. Holt Mark H. Johnson Johan Isaksson Prantik Kundu Meng-Chuan Lai Xavier Liogier D’ardhuy Michael V. Lombardo David J. Lythgoe René Mandl Andreas Meyer-Lindenberg Carolin Moessnang Nico Mueller Laurence O’Dwyer Marianne Oldehinkel Bob Oranje Gahan Pandina Antonio M. Persico Amber N. V. Ruigrok Barbara Ruggeri Jessica Sabet Roberto Sacco Antonia San José Cáceres Emily Simonoff Roberto Toro Heike Tost Jack Waldman Steve C. R. Williams Marcel P. Zwiers Will Spooren Declan G. M. Murphy Jan K. Buitelaar |
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Tony Charman Luke Mason Julian Tillmann Emily J. H. Jones Caroline Wooldridge Jumana Ahmad Bonnie Auyeung Claudia Brogna Sara Ambrosino Tobias Banaschewski Simon Baron-Cohen Sarah Baumeister Christian Beckmann Michael Brammer Daniel Brandeis Sven Bölte Thomas Bourgeron Carsten Bours Yvette de Bruijn Bhismadev Chakrabarti Daisy Crawley Ineke Cornelissen Flavio Dell’ Acqua Guillaume Dumas Sarah Durston Christine Ecker Jessica Faulkner Vincent Frouin Pilar Garces David Goyard Hannah Hayward Lindsay M. Ham Joerg Hipp Rosemary J. Holt Mark H. Johnson Johan Isaksson Prantik Kundu Meng-Chuan Lai Xavier Liogier D’ardhuy Michael V. Lombardo David J. Lythgoe René Mandl Andreas Meyer-Lindenberg Carolin Moessnang Nico Mueller Laurence O’Dwyer Marianne Oldehinkel Bob Oranje Gahan Pandina Antonio M. Persico Amber N. V. Ruigrok Barbara Ruggeri Jessica Sabet Roberto Sacco Antonia San José Cáceres Emily Simonoff Roberto Toro Heike Tost Jack Waldman Steve C. R. Williams Marcel P. Zwiers Will Spooren Declan G. M. Murphy Jan K. Buitelaar |
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