SUMMARY: zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available. AVAILABILITY: http://atguweb.mgh.harvard.edu/apps/zcall. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

SUMMARY: Here we present INRICH (INterval enRICHment analysis), a pathway-based genome-wide association analysis tool that tests for enriched association signals of predefined gene-sets across independent genomic intervals. INRICH has wide applicability, fast running time and, most importantly, robustness to potential genomic biases and confounding factors. Such factors, including varying gene size and single-nucleotide polymorphism density, linkage disequilibrium within and between genes and overlapping genes with similar annotations, are often not accounted for by existing gene-set enrichment methods. By using a genomic permutation procedure, we generate experiment-wide empirical significance values, corrected for the total number of sets tested, implicitly taking overlap of sets into account. By simulation we confirm a properly controlled type I error rate and reasonable power of INRICH under diverse parameter settings. As a proof of principle, we describe the application of INRICH on the NHGRI GWAS catalog. AVAILABILITY: A standalone C++ program, user manual and datasets can be freely downloaded from: http://atgu.mgh.harvard.edu/inrich/.

Abstract Summary: Although genetic association studies often test multiple, related phenotypes, few formal multivariate tests of association are available. We describe a test of association that can be efficiently applied to large population-based designs. Availability: A C++ implementation can be obtained from the authors. Contact: [email protected] Supplementary information: Supplementary figures are available at Bioinformatics online.

UNLABELLED: We describe a software tool to perform haplotype-based association analysis, for quantitative and qualitative traits, in population and family samples, using single nucleotide polymorphism or multiallelic marker data. A range of tests is offered: omnibus and haplotype-specific tests; prospective and retrospective likelihoods; covariates and moderators; sliding window analyses; permutation P-values. We focus on the ability to flexibly impose constraints on haplotype effects, which allows for a range of conditional haplotype-based likelihood ratio tests: for example, whether an allele has an effect independent of its haplotypic background, or whether a single variant can explain the overall association at a locus. We illustrate using these tests to dissect a multi-locus association. AVAILABILITY: WHAP is a C/C++ program, freely available from the author's website: http://pngu.mgh.harvard.edu/purcell/whap/

Abstract Summary: A website for performing power calculations for the design of linkage and association genetic mapping studies of complex traits. Availability: The package is made available athttp://statgen.iop.kcl.ac.uk/gpc/ Contact: [email protected] * To whom correspondence should be addressed.