Dissecting the Clinical Heterogeneity of Autism Spectrum Disorders through Defined Genotypes
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{"title"=>"Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes", "type"=>"journal", "authors"=>[{"first_name"=>"Hilgo", "last_name"=>"Bruining", "scopus_author_id"=>"35432317200"}, {"first_name"=>"Leo", "last_name"=>"de Sonneville", "scopus_author_id"=>"6701913540"}, {"first_name"=>"Hanna", "last_name"=>"Swaab", "scopus_author_id"=>"8296112400"}, {"first_name"=>"Maretha", "last_name"=>"de Jonge", "scopus_author_id"=>"7005631916"}, {"first_name"=>"Martien", "last_name"=>"Kas", "scopus_author_id"=>"6602425807"}, {"first_name"=>"Herman", "last_name"=>"van Engeland", "scopus_author_id"=>"7004512289"}, {"first_name"=>"Jacob", "last_name"=>"Vorstman", "scopus_author_id"=>"12344759400"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-77956503087", "sgr"=>"77956503087", "pui"=>"359515686", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"20526357", "doi"=>"10.1371/journal.pone.0010887"}, "id"=>"f06eb416-19ea-39db-975b-071903cbaae0", "abstract"=>"BACKGROUND: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. METHODOLOGY: The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. PRINCIPAL FINDINGS: The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. CONCLUSION: The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.", "link"=>"http://www.mendeley.com/research/dissecting-clinical-heterogeneity-autism-spectrum-disorders-through-defined-genotypes", "reader_count"=>68, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>5, "Student > Bachelor"=>6, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>5, "Student > Bachelor"=>6, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Agricultural and Biological Sciences"=>16, "Arts and Humanities"=>3, "Computer Science"=>2, "Earth and Planetary Sciences"=>1, "Energy"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>17, "Neuroscience"=>5, "Psychology"=>14, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>14}, "Unspecified"=>{"Unspecified"=>5}, "Arts and Humanities"=>{"Arts and Humanities"=>3}, "Engineering"=>{"Engineering"=>1}, "Neuroscience"=>{"Neuroscience"=>5}, "Energy"=>{"Energy"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Brazil"=>1, "Italy"=>1, "United Kingdom"=>1, "Germany"=>1, "Iceland"=>1, "Russia"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/847767"], "description"=>"<p>Domain S  =  Qualitative Abnormalities in Reciprocal Social Interaction, Domain C  =  Qualitative Abnormalities in Communication, Domain R  =  Restricted, Repetitive, and Stereotyped Patterns of Behavior.</p>", "links"=>[], "tags"=>["extracted", "adi-r", "items", "discriminant", "coefficients", "analyses", "22q11ds-asd", "ks-asd", "heterogeneous"], "article_id"=>518208, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.t004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_extracted_ADI_R_items_with_discriminant_function_coefficients_for_the_discriminant_analyses_of_22q11DS_ASD_and_KS_ASD_versus_heterogeneous_ASD_/518208", "title"=>"Description of extracted ADI-R items with discriminant function coefficients for the discriminant analyses of 22q11DS-ASD and KS-ASD versus heterogeneous ASD.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-28 02:16:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/847596"], "description"=>"<p>* <i>P</i><0.002, ** <i>P</i><0.0001, univariate analysis of variance.</p>", "links"=>[], "tags"=>["adi-r", "items", "autistic", "criterion"], "article_id"=>518043, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mean_number_of_ADI_R_items_reaching_autistic_criterion_ADI_R_score_8202_8202_2_/518043", "title"=>"Mean number of ADI-R items reaching autistic criterion (ADI-R score  =  2).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-28 02:14:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/421492", "https://ndownloader.figshare.com/files/421539", "https://ndownloader.figshare.com/files/421569", "https://ndownloader.figshare.com/files/421600", "https://ndownloader.figshare.com/files/421637", "https://ndownloader.figshare.com/files/421678"], "description"=>"<div><h3>Background</h3><p>The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile.</p><h3>Methodology</h3><p>The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles.</p><h3>Principal Findings</h3><p>The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population.</p><h3>Conclusion</h3><p>The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.</p></div>", "links"=>[], "tags"=>["dissecting", "heterogeneity", "autism", "disorders", "defined", "genotypes"], "article_id"=>143241, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0010887.s001", "https://dx.doi.org/10.1371/journal.pone.0010887.s002", "https://dx.doi.org/10.1371/journal.pone.0010887.s003", "https://dx.doi.org/10.1371/journal.pone.0010887.s004", "https://dx.doi.org/10.1371/journal.pone.0010887.s005", "https://dx.doi.org/10.1371/journal.pone.0010887.s006"], "stats"=>{"downloads"=>16, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dissecting_the_Clinical_Heterogeneity_of_Autism_Spectrum_Disorders_through_Defined_Genotypes/143241", "title"=>"Dissecting the Clinical Heterogeneity of Autism Spectrum Disorders through Defined Genotypes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-05-28 00:54:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/847816"], "description"=>"<p>Classification matrix of the discriminant analyses of 22q11DS-ASD and KS-ASD versus heterogeneous ASD through ADI-R labels and items respectively.</p>", "links"=>[], "tags"=>["matrix", "discriminant", "analyses", "22q11ds-asd", "ks-asd", "heterogeneous", "asd", "adi-r", "labels", "items"], "article_id"=>518261, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_matrix_of_the_discriminant_analyses_of_22q11DS_ASD_and_KS_ASD_versus_heterogeneous_ASD_through_ADI_R_labels_and_items_respectively_/518261", "title"=>"Classification matrix of the discriminant analyses of 22q11DS-ASD and KS-ASD versus heterogeneous ASD through ADI-R labels and items respectively.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-28 02:17:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/847686"], "description"=>"<p>22q11DS-ASD is predominantly discriminated from heterogeneous ASD by function 1, KS-ASD from heterogeneous ASD by function 2.</p>", "links"=>[], "tags"=>["canonical", "coefficients", "3-group", "discriminant", "heterogeneous", "asd", "22q11ds-asd", "ks-asd", "larger", "dots"], "article_id"=>518118, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.g002", "stats"=>{"downloads"=>1, "page_views"=>90, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plot_of_individual_subject_canonical_function_coefficients_of_the_3_group_discriminant_analysis_for_heterogeneous_ASD_grey_dots_versus_22q11DS_ASD_red_dots_versus_KS_ASD_blue_dots_the_larger_dots_represent_the_group_centroids_/518118", "title"=>"Plot of individual subject canonical function coefficients of the 3-group discriminant analysis for heterogeneous ASD (grey dots) versus 22q11DS-ASD (red dots) versus KS-ASD (blue dots), the larger dots represent the group centroids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-05-28 02:15:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/847910"], "description"=>"<p>KS-ASD  =  Klinefelter syndrome with Autism Spectrum Disorder, 22q11DS-ASD  =  22q11 deletion syndrome with Autism Spectrum Disorder. F =  Female, M = Male, TIQ =  average total IQ score.</p>", "links"=>[], "tags"=>["genetics and genomics/complex traits", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/medical genetics", "neuroscience/behavioral neuroscience"], "article_id"=>518356, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sample_characteristics_/518356", "title"=>"Sample characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-28 02:19:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/847862"], "description"=>"<p>Domain S  =  Qualitative Abnormalities in Reciprocal Social Interaction, Domain C  =  Qualitative Abnormalities in Communication, Domain R  =  Restricted, Repetitive, and Stereotyped Patterns of Behavior.</p>", "links"=>[], "tags"=>["extracted", "adi-r", "labels", "discriminant", "coefficients", "analyses", "22q11ds-asd", "ks-asd", "heterogeneous"], "article_id"=>518303, "categories"=>["Genetics", "Neuroscience"], "users"=>["Hilgo Bruining", "Leo de Sonneville", "Hanna Swaab", "Maretha de Jonge", "Martien Kas", "Herman van Engeland", "Jacob Vorstman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010887.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_extracted_ADI_R_labels_with_discriminant_function_coefficients_for_the_discriminant_analyses_of_22q11DS_ASD_and_KS_ASD_versus_heterogeneous_ASD_/518303", "title"=>"Description of extracted ADI-R labels with discriminant function coefficients for the discriminant analyses of 22q11DS-ASD and KS-ASD versus heterogeneous ASD.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2010-05-28 02:18:23"}

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