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Marker Locations (marker + locations)

Distribution by Scientific Domains
Mathematics and Statistics75%

Selected Abstracts

Score Statistic to Test for Genetic Correlation for Proband-Family Design

ANNALS OF HUMAN GENETICS, Issue 4 2005
R. El Galta
Summary In genetic epidemiological studies informative families are often oversampled to increase the power of a study. For a proband-family design, where relatives of probands are sampled, we derive the score statistic to test for clustering of binary and quantitative traits within families due to genetic factors. The derived score statistic is robust to ascertainment scheme. We considered correlation due to unspecified genetic effects and/or due to sharing alleles identical by descent (IBD) at observed marker locations in a candidate region. A simulation study was carried out to study the distribution of the statistic under the null hypothesis in small data-sets. To illustrate the score statistic, data from 33 families with type 2 diabetes mellitus (DM2) were analyzed. In addition to the binary outcome DM2 we also analyzed the quantitative outcome, body mass index (BMI). For both traits familial aggregation was highly significant. For DM2, also including IBD sharing at marker D3S3681 as a cause of correlation gave an even more significant result, which suggests the presence of a trait gene linked to this marker. We conclude that for the proband-family design the score statistic is a powerful and robust tool for detecting clustering of outcomes. [source]

Global Tests for Linkage

BIOMETRICAL JOURNAL, Issue 1 2009
Rachid el Galta
Abstract To test for global linkage along a genome or in a chromosomal region, the maximum over the marker locations of mean alleles shared identical by descent of affected relative pairs, Zmax, can be used. Feingold et al. (1993) derived a Gaussian approximation to the distribution of the Zmax. As an alternative we propose to sum over the observed marker locations along the chromosomal region of interest. Two test statistics can be derived. (1) The likelihood ratio statistic (LR) and (2) the corresponding score statistic. The score statistic appears to be the average mean IBD over all available marker locations. The null distribution of the LR and score tests are asymptotically a 50: 50 mixture of chi-square distributions of null and one degree of freedom and a normal distribution, respectively. We compared empirically the type I error and power of these two new test statistics and Zmax along a chromosome and in a candidate region. Two models were considered, namely (1) one disease locus and (2) two disease loci. The new test statistics appeared to have reasonable type I error. Along the chromosome, for both models we concluded that for very small effect sizes, the score test has slightly more power than the other test statistics. For large effect sizes, the likelihood ratio statistic was comparable to and sometimes performed better than Zmax and both test statistics performed much better than the score test. For candidate regions of about 30 cM, all test statistics were comparable when only one disease-locus existed and the score and likelihood ratio statistics had somewhat better power than Zmax when two disease loci existed (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Detecting Genomic Aberrations Using Products in a Multiscale Analysis

BIOMETRICS, Issue 3 2010
Xuesong Yu
Summary Genomic instability, such as copy-number losses and gains, occurs in many genetic diseases. Recent technology developments enable researchers to measure copy numbers at tens of thousands of markers simultaneously. In this article, we propose a nonparametric approach for detecting the locations of copy-number changes and provide a measure of significance for each change point. The proposed test is based on seeking scale-based changes in the sequence of copy numbers, which is ordered by the marker locations along the chromosome. The method leads to a natural way to estimate the null distribution for the test of a change point and adjusted,p -values for the significance of a change point using a step-down maxT permutation algorithm to control the family-wise error rate. A simulation study investigates the finite sample performance of the proposed method and compares it with a more standard sequential testing method. The method is illustrated using two real data sets. [source]