Genome-wide association tests of inversions with application to psoriasis. Hum Genet 2014 Aug;133(8):967-74
Date
03/14/2014Pubmed ID
24623382Pubmed Central ID
PMC4281304DOI
10.1007/s00439-014-1437-1Scopus ID
2-s2.0-84904414489 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Although inversions have occasionally been found to be associated with disease susceptibility through interrupting a gene or its regulatory region, or by increasing the risk for deleterious secondary rearrangements, no association study has been specifically conducted for risks associated with inversions, mainly because existing approaches to detecting and genotyping inversions do not readily scale to a large number of samples. Based on our recently proposed approach to identifying and genotyping inversions using principal components analysis (PCA), we herein develop a method of detecting association between inversions and disease in a genome-wide fashion. Our method uses genotype data for single nucleotide polymorphisms (SNPs), and is thus cost-efficient and computationally fast. For an inversion polymorphism, local PCA around the inversion region is performed to infer the inversion genotypes of all samples. For many inversions, we found that some of the SNPs inside an inversion region are fixed in the two lineages of different orientations and thus can serve as surrogate markers. Our method can be applied to case-control and quantitative trait association studies to identify inversions that may interrupt a gene or the connection between a gene and its regulatory agents. Our method also offers a new venue to identify inversions that are responsible for disease-causing secondary rearrangements. We illustrated our proposed approach to case-control data for psoriasis and identified novel associations with a few inversion polymorphisms.
Author List
Ma J, Xiong M, You M, Lozano G, Amos CIMESH terms used to index this publication - Major topics in bold
Case-Control StudiesChromosome Inversion
Genome, Human
Genome-Wide Association Study
Haplotypes
Humans
Models, Genetic
Polymorphism, Genetic
Principal Component Analysis
Psoriasis