Biomedical subjects

Brian L Browning

Publications and source records attributed to Brian L Browning.

3 recordsLinked to original sources

PubMed2005

Evaluation of Nyholt's procedure for multiple testing correction.

OBJECTIVE: A simple method for accounting efficiently for multiple testing of many SNPs in an association study was recently proposed by Nyholt, but its performance was not extensively evaluated. The method involves estimating an 'effective number' of independent tests and then adjusting the smallest observed p value using Sidák's formula based on this number of tests. We sought to carry out an empirical and theoretical evaluation of Nyholt's method. METHODS: Nyholt's method was applied to a sample of 31 genes typed at a total of 291 SNPs and permutation used to determine the type-I error rate for each gene. Based on our empirical results, we algebraically investigated the effective number of independent tests for a simple model of haplotype block structure. RESULTS: The nominal 5% type I error rate varied from under 3% to over 7%, and was dependent on linkage disequilibrium. Theoretical considerations show further that the method can be very conservative in the presence of haplotype block structure. CONCLUSION: Although Nyholt's approach may be useful as an exploratory tool, it is not an adequate substitute for permutation tests.

Case-Control Studies↗

PubMed2004

Linkage analysis using single nucleotide polymorphisms.

We performed multipoint linkage analysis using 83 markers from the SNP Consortium (TSC) SNP linkage map in 3 regions covering 190 cM previously scanned with microsatellite markers and found to be linked to type 2 diabetes. Since the average linkage disequilibrium present in the TSC SNP marker clusters is relatively low, we assumed the intracluster genetic distances were a reasonable small nonzero distance (0.03 cM) and performed linkage analysis using GENEHUNTER PLUS and ASM linkage analysis software. We found that for the pedigree structures and missing data patterns in our samples the average information content in all three regions and the LOD score curves in two regions obtained from the TSC SNP markers were similar to results obtained from microsatellite marker maps with 10 cM average spacing. We also give an algorithm which extends the Lander-Green algorithm to permit multipoint linkage analysis of clusters of tightly linked markers with arbitrarily high levels of intracluster linkage disequilibrium.

Chromosome Mapping↗

PubMed2002

On reducing the statespace of hidden Markov models for the identity by descent process.

Important methods for calculating likelihoods of genealogical relationships and mapping genes are based on hidden Markov models for the process of identity by descent along chromosomes. The computational time for the algorithms depends critically on the size of the statespace of the hidden Markov model. We describe the maximal grouping together of states of the model to reduce the size of the statespace. This grouping is based on pedigree symmetries. We also present an efficient algorithm for finding the maximal grouping.

Algorithms↗