ABSTRACT
In the analysis of DNA sequences on related individuals, most methods strive to incorporate as much information as possible, with little or no attention paid to the issue of statistical significance. For example, a modern workstation can easily handle the computations needed to perform a large-scale genome-wide inheritance-by-descent (IBD) scan, but accurate assessment of the significance of that scan is often hindered by inaccurate approximations and computationally intensive simulation. To address these issues, we developed gLOD-a test of co-segregation that, for large samples, models chromosome-specific IBD statistics as a collection of stationary Gaussian processes. With this simple model, the parametric bootstrap yields an accurate and rapid assessment of significance-the genome-wide corrected P-value. Furthermore, we show that (i) under the null hypothesis, the limiting distribution of the gLOD is the standard Gumbel distribution; (ii) our parametric bootstrap simulator is approximately 40 000 times faster than gene-dropping methods, and it is more powerful than methods that approximate the adjusted P-value; and, (iii) the gLOD has the same statistical power as the widely used maximum Kong and Cox LOD. Thus, our approach gives researchers the ability to determine quickly and accurately the significance of most large-scale IBD scans, which may contain multiple traits, thousands of families and tens of thousands of DNA sequences.
Subject(s)
Computer Simulation , Genomics/methods , Models, Genetic , Humans , Microsatellite Repeats , Models, StatisticalABSTRACT
In order to investigate the long-term effect of clinical rehabilitation measures as well as the additional effect of prescription of a special pillow in patients suffering from chronic cervicobrachialgia a total of 149 patients was investigated. All patients suffered from chronic cervicobrachialgia and were admitted for rehabilitative treatment in the orthopaedic Elfenmaar-Klinik of Bad Bertrich. For a four-week period the patients were treated with physical therapy including gymnastics, electrotherapy, thermotherapy, and massage. Additionally they underwent a health-promoting programme specially designed for patients with spondylopathia. The patients were randomly divided into two groups, one receiving a special pillow (Curavario, Pala-Medic-Company) for the use during and after the rehabilitative treatment (n = 76 or n = 73, respectively). For two weeks before the treatment, during the four-week treatment period and for two weeks after the treatment the patients had to fill in a questionnaire, comprising among others six questions on the intensity of their cervicobrachialgic symptoms (pain-intensity [local pain, radiation of pain], muscular tenseness, paraesthesia and sleep disorders [caused by pain or paraesthesia]). Three, six, and nine month after the treatment period the patients received a similar questionnaire. Immediately after the treatment period a significant reduction of mean pain intensity and muscle tenseness (p < 0.001; Rep.-Mes.-ANOVA) was found. At the same time significantly lower frequencies of pain radiation and sleep disorders caused by pain or paraesthesia (p < 0.001; chi-square-test) were found. During the following nine months the intensity of the symptoms slightly re-increased, however, all parameters were still reduced nine months after treatment compared to the values before treatment (p < 0.01). Before and during the treatment no difference between the two groups could be detected, however, the follow-up showed significantly lower scores of pain intensity (p < 0.05; Student-t-test) and sleep disorders (p < 0.01; chi-square test) in the patients who had received the special pillow. It is concluded that the rehabilitative treatment is effective in patients suffering from chronic cervicobrachialgia and that the complaints in the post-treatment period can be reduced by prescription of special pillows.
