Genetic-linkage mapping of complex hereditary disorders to a whole-genome molecular-interaction network.
Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that contribute to common heritable disorders. We apply the model to three large genotype-phenotype data sets, identify a small number of significant candidate genes for autism (24), bipolar disorder (21), and schizophrenia (25), and predict a number of gene targets likely to be shared among the disorders.
Iossifov
Ivan
I
Department of Biomedical Informatics, Center for Computational Biology and Bioinformatics, Columbia University, New York, New York 10032, USA.
Zheng
Tian
T
Baron
Miron
M
Gilliam
T Conrad
TC
Rzhetsky
Andrey
A
D001321:Autistic Disorder / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics