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Motivation: The development of Approximate Bayesian Computation (ABC) algorithms for parameter inference which are both computationally efficient and scalable in parallel computing environments is an important area of research. Monte Carlo rejection sampling, a fundamental component of ABC algorithms, is trivial to distribute over multiple processors but is inherently inefficient. While development of algorithms such as ABC Sequential Monte Carlo (ABC-SMC) help address the inherent inefficiencies of rejection sampling, such approaches are not as easily scaled on multiple processors. As a result, current Bayesian inference software offerings that use ABC-SMC lack the ability to scale in parallel computing environments., Results: We present al3c, a C++ framework for implementing ABC-SMC in parallel. By requiring only that users define essential functions such as the simulation model and prior distribution function, al3c abstracts the user from both the complexities of parallel programming and the details of the ABC-SMC algorithm. By using the al3c framework, the user is able to scale the ABC-SMC algorithm in parallel computing environments for his or her specific application, with minimal programming overhead., Availability and Implementation: al3c is offered as a static binary for Linux and OS-X computing environments. The user completes an XML configuration file and C++ plug-in template for the specific application, which are used by al3c to obtain the desired results. Users can download the static binaries, source code, reference documentation and examples (including those in this article) by visiting https://github.com/ahstram/al3c., Contact: astram@usc.edu, Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

Motivation: In modern sequencing studies, one can improve the confidence of genotype calls by phasing haplotypes using information from an external reference panel of fully typed unrelated individuals. However, the computational demands are so high that they prohibit researchers with limited computational resources from haplotyping large-scale sequence data., Results: Our graphics processing unit based software delivers haplotyping and imputation accuracies comparable to competing programs at a fraction of the computational cost and peak memory demand., Availability: Mendel-GPU, our OpenCL software, runs on Linux platforms and is portable across AMD and nVidia GPUs. Users can download both code and documentation at http://code.google.com/p/mendel-gpu/., Contact: gary.k.chen@usc.edu., Supplementary Information: Supplementary data are available at Bioinformatics online.

I seek to comprehensively evaluate the quality of the Genetic Analysis Workshop 17 (GAW17) data set by examining the accuracy of its genotype calls, which were based on the pilot3 data of the 1000 Genomes Project. Taking advantage of the 1000 Genomes Project/HapMap sample intersect, I compared GAW17 genotype calls to HapMap III, release 2, genotype calls for an individual. These genotype calls should be concordant almost everywhere. Instead I found an astonishingly low 65.4% concordance. Regarding HapMap as the gold standard, I assume that this is a GAW17 data problem and seek to explain this discordance accordingly. I found that a large proportion of this discordance occurred outside targeted regions and that concordance could be improved to at least 94.6% by simply staying within targeted regions, which were sequenced across more samples. Furthermore, I found that in certain individuals, high sample counts did little to improve concordance and concluded that quality scores for a certain sample's sequence reads were simply incorrect.

Adult height is a classic polygenic trait of high heritability (h(2) approximately 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain approximately10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10(-12) and 2p14-rs4315565, P = 1.2×10(-8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10(-4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits., Competing Interests: The authors have declared that no competing interests exist.