TY - JOUR
T1 - The EU-AIMS Longitudinal European Autism Project (LEAP)
T2 - Design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders
AU - Loth, Eva
AU - Charman, Tony
AU - Mason, Luke
AU - Tillmann, Julian
AU - Jones, Emily J. H.
AU - Wooldridge, Caroline
AU - Ahmad, Jumana
AU - Auyeung, Bonnie
AU - Brogna, Claudia
AU - Ambrosino, Sara
AU - Banaschewski, Tobias
AU - Baron-Cohen, Simon
AU - Baumeister, Sarah
AU - Beckmann, Christian
AU - Brammer, Michael
AU - Brandeis, Daniel
AU - Bölte, Sven
AU - Bourgeron, Thomas
AU - Bours, Carsten
AU - De Bruijn, Yvette
AU - Chakrabarti, Bhismadev
AU - Crawley, Daisy
AU - Cornelissen, Ineke
AU - Dell' Acqua, Flavio
AU - Dumas, Guillaume
AU - Durston, Sarah
AU - Ecker, Christine
AU - Faulkner, Jessica
AU - Frouin, Vincent
AU - Garces, Pilar
AU - Goyard, David
AU - Hayward, Hannah
AU - Ham, Lindsay M.
AU - Hipp, Joerg
AU - Holt, Rosemary J.
AU - Johnson, Mark H.
AU - Isaksson, Johan
AU - Kundu, Prantik
AU - Lai, Meng Chuan
AU - D'ardhuy, Xavier Liogier
AU - Lombardo, Michael V.
AU - Lythgoe, David J.
AU - Mandl, René
AU - Meyer-Lindenberg, Andreas
AU - Moessnang, Carolin
AU - Mueller, Nico
AU - O'Dwyer, Laurence
AU - Oldehinkel, Marianne
AU - Oranje, Bob
AU - Pandina, Gahan
AU - Persico, Antonio M.
AU - Ruigrok, Amber N. V.
AU - Ruggeri, Barbara
AU - Sabet, Jessica
AU - Sacco, Roberto
AU - Cáceres, Antonia San José
AU - Simonoff, Emily
AU - Toro, Roberto
AU - Tost, Heike
AU - Waldman, Jack
AU - Williams, Steve C. R.
AU - Zwiers, Marcel P.
AU - Spooren, Will
AU - Murphy, Declan G. M.
AU - Buitelaar, Jan K.
PY - 2017/6/23
Y1 - 2017/6/23
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Cognition
KW - EEG
KW - Eye-tracking
KW - Genetics
KW - MRI
KW - Neuroimaging
UR - http://www.scopus.com/inward/record.url?scp=85021086460&partnerID=8YFLogxK
U2 - 10.1186/s13229-017-0146-8
DO - 10.1186/s13229-017-0146-8
M3 - Article
AN - SCOPUS:85021086460
SN - 2040-2392
VL - 8
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 24
ER -