Linkage and Association Studies of Joint Morbidity from Rheumatoid Arthritis

Min, Jin‐Young; Min, Kyoung-Bok; Sung, Joohon; Cho, Sung-Il

doi:10.3899/jrheum.090526

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Figure 1 gives the Haploview LD display for this haplotype block. On the other hand, Min et al [26] reported that chromosome 15p34 at rs347117 showed a possible linkage peak to RA by using the nonparametric linkage score (), which may support our finding.…”

Section: Resultssupporting

confidence: 89%

Powerful Haplotype-Based Hardy-Weinberg Equilibrium Tests for Tightly Linked Loci

Mao

et al. 2013

PLoS ONE

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Recently, there have been many case-control studies proposed to test for association between haplotypes and disease, which require the Hardy-Weinberg equilibrium (HWE) assumption of haplotype frequencies. As such, haplotype inference of unphased genotypes and development of haplotype-based HWE tests are crucial prior to fine mapping. The goodness-of-fit test is a frequently-used method to test for HWE for multiple tightly-linked loci. However, its degrees of freedom dramatically increase with the increase of the number of loci, which may lack the test power. Therefore, in this paper, to improve the test power for haplotype-based HWE, we first write out two likelihood functions of the observed data based on the Niu's model (NM) and inbreeding model (IM), respectively, which can cause the departure from HWE. Then, we use two expectation-maximization algorithms and one expectation-conditional-maximization algorithm to estimate the model parameters under the HWE, IM and NM models, respectively. Finally, we propose the likelihood ratio tests LRT and LRT for haplotype-based HWE under the NM and IM models, respectively. We simulate the HWE, Niu's, inbreeding and population stratification models to assess the validity and compare the performance of these two LRT tests. The simulation results show that both of the tests control the type I error rates well in testing for haplotype-based HWE. If the NM model is true, then LRT is more powerful. While, if the true model is the IM model, then LRT has better performance in power. Under the population stratification model, LRT is still more powerful. To this end, LRT is generally recommended. Application of the proposed methods to a rheumatoid arthritis data set further illustrates their utility for real data analysis.

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Section: Resultssupporting

confidence: 89%