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D V Zaykin

Publications and source records attributed to D V Zaykin.

4 recordsLinked to original sources
PubMed2002

Truncated product method for combining P-values.

We present a new procedure for combining P-values from a set of L hypothesis tests. Our procedure is to take the product of only those P-values less than some specified cut-off value and to evaluate the probability of such a product, or a smaller value, under the overall hypothesis that all L hypotheses are true. We give an explicit formulation for this P-value, and find by simulation that it can provide high power for detecting departures from the overall hypothesis. We extend the procedure to situations when tests are not independent. We present both real and simulated examples where the method is especially useful. These include exploratory analyses when L is large, such as genome-wide scans for marker-trait associations and meta-analytic applications that combine information from published studies, with potential for dealing with the "publication bias" phenomenon. Once the overall hypothesis is rejected, an adjustment procedure with strong family-wise error protection is available for smaller subsets of hypotheses, down to the individual tests.

Genetic Linkage↗
PubMed2001

Identifying susceptibility genes using linkage and linkage disequilibrium analysis in large pedigrees.

Linkage and linkage disequilibrium tests are powerful tools for mapping complex disease genes. We investigated two approaches to identifying markers associated with disease. One method applied linkage analysis and then linkage disequilibrium tests to markers within linked regions. The other method looked for linkage disequilibrium with disease using all markers. Additionally, we investigated using Simes' test to combine p-values from linkage disequilibrium tests for nearby markers. We applied both approaches to all replicates of the Genetic Analysis Workshop 12 problem 2 isolated population data set. We reported results from the 25th replicate as if it were a real problem and assessed the power of our methods using all replicates. Using all replicates, we found that testing all markers for linkage disequilibrium with disease was more powerful than identifying markers that were in linkage with disease and then testing markers within those regions for linkage disequilibrium with the implementations that we chose. Using Simes' test to combine p-values for linkage disequilibrium tests on correlated markers seemed to be of marginal value.

Chromosome Mapping↗
PubMed1996

On the potential for estimating the effective number of breeders from heterozygote-excess in progeny.

The important parameter of effective population size is rarely estimable directly from demographic data. Indirect estimates of effective population size may be made from genetic data such as temporal variation of allelic frequencies or linkage disequilibrium in cohorts. We suggest here that an indirect estimate of the effective number of breeders might be based on the excess of heterozygosity expected in a cohort of progeny produced by a limited number of males and females. In computer simulations, heterozygote excesses for 30 unlinked loci having various numbers of alleles and allele-frequency profiles were obtained for cohorts produced by samples of breeders drawn form an age-structured population and having known variance in reproductive success and effective number. The 95% confidence limits around the estimate contained the true effective population size in 70 of 72 trials and the Spearman rank correlation of estimated and actual values was 0.991. An estimate based on the heterozygote excess might have certain advantages over the previous estimates, requiring only single-locus and single-cohort data, but the sampling error among individuals and the effect of departures from random union of gametes still need to be explored.

Breeding↗