Dataset Information

Incorporating multiple-marker information to detect risk loci for rheumatoid arthritis.

ABSTRACT: In genome-wide association studies, new schemes are needed to incorporate multiple-locus information. In this article, we proposed a two-stage sliding-window approach to detect associations between a disease and multiple genetic polymorphisms. In the proposed approach, we measured the genetic association between a disease and a single-nucleotide polymorphism window by the newly developed likelihood ratio test-principal components statistic, and performed a sliding-window technique to detect disease susceptibility windows. We split the whole sample into two sub-samples, each of which contained a portion of cases and controls. In the first stage, we selected the top R windows by the statistics based on the first sub-sample, and in the second stage, we claimed significant windows by false-discovery rate correction on the p-values of the statistics based on the second sub-sample. By applying the new approach to the Genetic Analysis Workshop 16 Problem 1 data set, we detected 212 out of 531,601 windows to be responsible for rheumatoid arthritis. Except for chromosomes 4 and 18, each of the other 20 autosomes was found to harbor risk windows. Our results supported the findings of some rheumatoid arthritis susceptibility genes identified in the literature. In addition, we identified several new single-nucleotide polymorphism windows for follow-up studies.

SUBMITTER: Wang X

PROVIDER: S-EPMC2795925 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Incorporating multiple-marker information to detect risk loci for rheumatoid arthritis.

Wang Xuexia X Qin Huaizhen H Sha Qiuying Q

BMC proceedings 20091215

In genome-wide association studies, new schemes are needed to incorporate multiple-locus information. In this article, we proposed a two-stage sliding-window approach to detect associations between a disease and multiple genetic polymorphisms. In the proposed approach, we measured the genetic association between a disease and a single-nucleotide polymorphism window by the newly developed likelihood ratio test-principal components statistic, and performed a sliding-window technique to detect dise ...[more]

PMID: 20018018

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Project description:ObjectivePatients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms; this can be done by screening patients with the use of chest high-resolution computed tomography (HRCT). Our objective was to develop and validate a risk score for patients who have subclinical RA-ILD.MethodsOur study included a discovery population and a replication population from 2 prospective RA cohorts (ESPOIR and TRANSLATE2, respectively) without pulmonary symptoms who had received chest HRCT scans. All patients were genotyped for MUC5B rs35705950. After multiple logistic regression, a risk score based on independent risk factors for subclinical RA-ILD was developed in the discovery population and tested for validation in the replication population.ResultsThe discovery population included 163 patients with RA, and the replication population included 89 patients with RA. The prevalence of subclinical RA-ILD was 19.0% and 16.9%, respectively. In the discovery population, independent risk factors for subclinical RA-ILD were presence of the MUC5B rs35705950 T allele (odds ratio [OR] 3.74 [95% confidence interval (95% CI) 1.37, 10.39]), male sex (OR 3.93 [95% CI 1.40, 11.39]), older age at RA onset (for each year, OR 1.10 [95% CI 1.04, 1.16]), and increased mean Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (for each unit, OR 2.03 [95% CI 1.24, 3.42]). We developed and validated a derived risk score with receiver operating characteristic areas under the curve of 0.82 (95% CI 0.70-0.94) for the discovery population and 0.78 (95% CI 0.65-0.92) for the replication population. Excluding MUC5B rs35705950 from the model provided a lower goodness of fit (likelihood ratio test, P = 0.01).ConclusionWe developed and validated a risk score that could help identify patients at high risk of subclinical RA-ILD. Our findings support an important contribution of MUC5B rs35705950 to subclinical RA-ILD risk.

Project description:Rapid development of intelligent information equipment accelerates the expansion of mobile social network. Speed of information spreading is gradually growing, there are lots of changes in the scale and mode of information spreading. But the basic communication network is not developed and not mature, when online information platforms breakdown sometimes it happens to be when important information appears. Therefore, the research is done to solve these occasion problems, help network information platform filter hot news and discuss the reason that hot news exists longer than other news in the Internet. In this paper, a multiple information propagation model incorporating both local information environment and people's limited attention is proposed based on Susceptible Infected Recovered (SIR) model. Two new concepts are introduced into the model: heat rate and popular rate, to measure the local information influence power and people's limited attention to information respectively, which are key factors determining node state transformation instead of fixed probability. In order to analyze the influence from limited attention, a situation is designed that several pieces of information are popular successively. The theoretical analysis shows that the early popular information gets more attention than the later popular information, and more attention makes it easier to spread. Besides, numerical simulation is conducted in both uniform network and scale-free network. The simulation results show that the early popular information is less vulnerable to the increase of information acceptance threshold and more sensitive to the decrease of information rejection threshold than the later popular information. Moreover, the model can also be used in the case of large amount of information transmission without adding too much complexity. Reasons are given in the research that the top hot news exists very much longer than the other ones, and latter news which have same influence as top news are hard to get the same focus. Meanwhile, results in the research can provide some ways for the other researches in the related fields. They also help related information platforms to filter and push news and referable strategies to maintain hot news.

Dataset Information

Incorporating multiple-marker information to detect risk loci for rheumatoid arthritis.

Publications

Incorporating multiple-marker information to detect risk loci for rheumatoid arthritis.

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