Title
On the simultaneous association analysis of large genomic regions: a massive multi-locus association test.
Abstract
Motivation: For samples of unrelated individuals, we propose a general analysis framework in which hundred thousands of genetic loci can be tested simultaneously for association with complex phenotypes. The approach is built on spatial-clustering methodology, assuming that genetic loci that are associated with the target phenotype cluster in certain genomic regions. In contrast to standard methodology for multilocus analysis, which has focused on the dimension reduction of the data, our multilocus association-clustering test profits from the availability of large numbers of genetic loci by detecting clusters of loci that are associated with the phenotype. Results: The approach is computationally fast and powerful, enabling the simultaneous association testing of large genomic regions. Even the entire genome or certain chromosomes can be tested simultaneously. Using simulation studies, the properties of the approach are evaluated. In an application to a genome-wide association study for chronic obstructive pulmonary disease, we illustrate the practical relevance of the proposed method by simultaneously testing all genotyped loci of the genome-wide association study and by testing each chromosome individually. Our findings suggest that statistical methodology that incorporates spatial-clustering information will be especially useful in whole-genome sequencing studies in which millions or billions of base pairs are recorded and grouped by genomic regions or genes, and are tested jointly for association.
Year
DOI
Venue
2014
10.1093/bioinformatics/btt654
BIOINFORMATICS
Field
DocType
Volume
Genome,Genotype,Candidate gene,Biology,Genome-wide association study,Genomics,Genetic association,Bioinformatics,Locus (genetics),Genetic marker
Journal
30
Issue
ISSN
Citations 
2
1367-4803
1
PageRank 
References 
Authors
0.36
3
7
Name
Order
Citations
PageRank
Dandi Qiao1130.96
Michael H Cho2144.95
Heide Fier351.54
Per S Bakke410.36
Amund Gulsvik510.36
Edwin K. Silverman6587.75
Christoph Lange716320.58