Genome-wide association study of rheumatoid arthritis by a score test based on wavelet transformation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

We have conducted a genome-wide association study on the Genetic Analysis Workshop (GAW) 16 rheumatoid arthritis data using a multilocus score test based on wavelet transform proposed recently by the authors. The wavelet-based test automatically adjusts for the amount of noise suppressed from the data. The power of the test is also increased by using the genetic information contained in the spatial ordering of single-nucleotide polymorphisms on a chromosome.

Results

After adjusting for the effect of population stratification, the test identified some previously discovered rheumatoid arthritis susceptibility loci ( HLA-DRB1 and rs3761847) as well as some loci (rs2076530 and rs3130340) known to have association with sarcoidosis and bone mineral density. It was previously reported that patients with rheumatoid arthritis have elevated prevalence of sarcoidosis and have reduced bone mass.

Conclusion

This new test provides a useful tool in genome-wide association studies.

Related collections

Most cited references 15

Record: found
Abstract: found
Article: not found

A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase.

Paul Scheet, Matthew Stephens (2006)

We present a statistical model for patterns of genetic variation in samples of unrelated individuals from natural populations. This model is based on the idea that, over short regions, haplotypes in a population tend to cluster into groups of similar haplotypes. To capture the fact that, because of recombination, this clustering tends to be local in nature, our model allows cluster memberships to change continuously along the chromosome according to a hidden Markov model. This approach is flexible, allowing for both "block-like" patterns of linkage disequilibrium (LD) and gradual decline in LD with distance. The resulting model is also fast and, as a result, is practicable for large data sets (e.g., thousands of individuals typed at hundreds of thousands of markers). We illustrate the utility of the model by applying it to dense single-nucleotide-polymorphism genotype data for the tasks of imputing missing genotypes and estimating haplotypic phase. For imputing missing genotypes, methods based on this model are as accurate or more accurate than existing methods. For haplotype estimation, the point estimates are slightly less accurate than those from the best existing methods (e.g., for unrelated Centre d'Etude du Polymorphisme Humain individuals from the HapMap project, switch error was 0.055 for our method vs. 0.051 for PHASE) but require a small fraction of the computational cost. In addition, we demonstrate that the model accurately reflects uncertainty in its estimates, in that probabilities computed using the model are approximately well calibrated. The methods described in this article are implemented in a software package, fastPHASE, which is available from the Stephens Lab Web site.

0 comments Cited 754 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Score tests for association between traits and haplotypes when linkage phase is ambiguous.

Daniel J. Schaid, Charles M. Rowland, David E Tines … (2002)

A key step toward the discovery of a gene related to a trait is the finding of an association between the trait and one or more haplotypes. Haplotype analyses can also provide critical information regarding the function of a gene; however, when unrelated subjects are sampled, haplotypes are often ambiguous because of unknown linkage phase of the measured sites along a chromosome. A popular method of accounting for this ambiguity in case-control studies uses a likelihood that depends on haplotype frequencies, so that the haplotype frequencies can be compared between the cases and controls; however, this traditional method is limited to a binary trait (case vs. control), and it does not provide a method of testing the statistical significance of specific haplotypes. To address these limitations, we developed new methods of testing the statistical association between haplotypes and a wide variety of traits, including binary, ordinal, and quantitative traits. Our methods allow adjustment for nongenetic covariates, which may be critical when analyzing genetically complex traits. Furthermore, our methods provide several different global tests for association, as well as haplotype-specific tests, which give a meaningful advantage in attempts to understand the roles of many different haplotypes. The statistics can be computed rapidly, making it feasible to evaluate the associations between many haplotypes and a trait. To illustrate the use of our new methods, they are applied to a study of the association of haplotypes (composed of genes from the human-leukocyte-antigen complex) with humoral immune response to measles vaccination. Limited simulations are also presented to demonstrate the validity of our methods, as well as to provide guidelines on how our methods could be used.

0 comments Cited 336 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.

Robert Plenge, Mark Seielstad, Leonid Padyukov … (2007)

Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P<1x10(-8)) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P=4x10(-14)). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. Copyright 2007 Massachusetts Medical Society.

0 comments Cited 235 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Conference

Journal ID (nlm-ta): BMC Proc

Title: BMC Proceedings

Publisher: BioMed Central

ISSN (Electronic): 1753-6561

Publication date Collection: 2009

Publication date (Electronic): 15 December 2009

Volume: 3

Issue: Suppl 7

Page: S8

Affiliations

[1 ]Department of Mathematical Sciences, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA

Article

Publisher ID: 1753-6561-3-S7-S8

PMC ID: 2795982

PubMed ID: 20018075

SO-VID: 6e655c8f-3e31-454a-83e5-b4b94acd5717

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome-wide association study of rheumatoid arthritis by a score test based on wavelet transformation

Read this article at

Abstract

Background

Results

Conclusion

Related collections

Point-of-Care Testing for COVID-19

Most cited references 15

A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase.

Score tests for association between traits and haplotypes when linkage phase is ambiguous.

TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.

Author and article information

Conference

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 518

Cited by 2

Most referenced authors 238