alexa Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised
ISSN: 2165-7890

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Research Article

Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Ulrika Roine1*, Samuli Ripatti2,3,4, Karola Rehnström3, Timo Roine5, Helena Kilpinen3, Ida Surakka2, Juho Wedenoja2, Tero Ylisaukko-oja2,6, Elli Kempas2, Jaana Wessman2, Irma Moilanen7, Marja-Leena Mattila7, Marko Kielinen7, Katja Jussila7, Saara Suomalainen8, Esko Pulkkinen9, Lennart von Wendt10 and Leena Peltonen2,3

1Department of Biomedical Engineering and Computational Science, Aalto University School of Science, P.O. Box 12200, FI-00076 AALTO, Finland

2Institute for Molecular Medicine Finland, Human Genomics, Helsinki, Finland

3Wellcome Trust Sanger Institute, Human Genetics, Cambridge, United Kingdom

4Hjelt Institute, University of Helsinki, Finland

5Department of Automation and Systems Technology, Aalto University, Espoo, Finland

6Institute of Health Sciences (General Practice), University of Oulu, Finland

7Clinic of Child Psychiatry, University of Oulu, Finland

8Lapland Hospital District, Rovaniemi, Finland

9Clinic of Psychiatry, Pieksämäki, Finland

10Hospital for Children and Adolescents, Unit of Child Neurology, Helsinki, Finland

*Corresponding Author:
Ulrika Roine, M.D., M.Sc.
Department of Biomedical Engineering and Computational Science
Aalto University School of Science, P.O. Box 12200
FI-00076 AALTO, Finland
Tel: +358 50 571 0003
E-mail: [email protected]

Received date December 15, 2012; Accepted date January 29, 2013; Published date February 11, 2013

Citation: Roine U, Ripatti S, Rehnström K, Roine T, Kilpinen H, et al. (2013) Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised. Autism 3:107. doi:10.4172/2165-7890.1000107

Copyright: © 2013 Roine U, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


 

Abstract

Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.

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