Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited po...

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Bibliographic Details
Published in:Genetics (Austin) 2016-08, Vol.203 (4), p.1901-1913
Main Authors: Rohde, Palle Duun, Demontis, Ditte, Cuyabano, Beatriz Castro Dias, Børglum, Anders D, Sørensen, Peter
Format: Article
Language:English
Subjects:
Computer Simulation
Consortia
Disease
Economic models
Gene expression
Genome, Human
Genome-Wide Association Study - statistics & numerical data
Genomes
Genomics
Humans
Immunology
Investigations
Life Sciences
Models, Genetic
Polymorphism, Single Nucleotide - genetics
Schizophrenia
Schizophrenia - genetics
Schizophrenia - metabolism
Schizophrenia - pathology
Statistics
Studies
Test methods
Vitamin A - genetics
Vitamin A - metabolism
Working groups
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Summary:Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1534/genetics.116.189498