Network assisted analysis to reveal the genetic basis of autism

DOI10.1214/15-AOAS844zbMATH Open1454.62354arXiv1506.00728OpenAlexW583919932WikidataQ39804773 ScholiaQ39804773MaRDI QIDQ902933FDOQ902933

Authors: Li Liu, Jing Lei, Kathryn Roeder 

Publication date: 4 January 2016

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: While studies show that autism is highly heritable, the nature of the genetic basis of this disorder remains illusive. Based on the idea that highly correlated genes are functionally interrelated and more likely to affect risk, we develop a novel statistical tool to find more potentially autism risk genes by combining the genetic association scores with gene co-expression in specific brain regions and periods of development. The gene dependence network is estimated using a novel partial neighborhood selection (PNS) algorithm, where node specific properties are incorporated into network estimation for improved statistical and computational efficiency. Then we adopt a hidden Markov random field (HMRF) model to combine the estimated network and the genetic association scores in a systematic manner. The proposed modeling framework can be naturally extended to incorporate additional structural information concerning the dependence between genes. Using currently available genetic association data from whole exome sequencing studies and brain gene expression levels, the proposed algorithm successfully identified 333 genes that plausibly affect autism risk.

Full work available at URL: https://arxiv.org/abs/1506.00728

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zbMATH Keywords

hidden Markov random fieldnetwork estimationautism spectrum disorderneighborhood selectionrisk gene discovery

Mathematics Subject Classification ID

Markov processes: estimation; hidden Markov models (62M05) Random fields; image analysis (62M40) Applications of statistics to biology and medical sciences; meta analysis (62P10)

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• Network assisted analysis to reveal the genetic basis of autism

Cited In (8)

• Data-adaptive multi-locus association testing in subjects with arbitrary genealogical relationships
• Logistic regression augmented community detection for network data with application in identifying autism-related gene pathways
• Covariance-based sample selection for heterogeneous data: applications to gene expression and autism risk gene detection
• An intelligent multimodal framework for identifying children with autism spectrum disorder
• Prioritizing Autism Risk Genes Using Personalized Graphical Models Estimated From Single-Cell RNA-seq Data
• Using game theory to detect genes involved in autism spectrum disorder
• Mining susceptibility gene modules and disease risk genes from SNP data by combining network topological properties with support vector regression
• Network assisted analysis to reveal the genetic basis of autism

Uses Software

• WGCNA
• glasso
• hglasso
• HotNet

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