Tag: Rare Variant


[PMID: 28669402] [American Journal of Human Genetics]

SEQSpark: A Complete Analysis Tool for Large-Scale Rare Variant Association Studies using Whole-Genome and Exome Sequence Data

“implements parallel processing based on Spark to increase the speed and efficiency of performing data quality control, annotation, and association analysis.”


Rare Variants in Common Disease

[PMID:28449691] [Genome Biology]

The impact of rare and low-frequency genetic variants in common disease 

“review the current state of knowledge from rare variant association studies (RVASs) of complex traits and review approaches for discovering and testing associations for rare variants.”

Rare Variants on Complex Traits May Be Premature

[PMID:27197206] [Genome Research]

Selection and explosive growth alter genetic architecture and hamper the detection of causal rare variants
“most rare variant association tests (RVATs) do not account for the evolutionary forces that affect genetic architecture””we use simulation and numerical algorithms to show that explosive population growth, as experienced by human populations, can dramatically increase the impact of very rare alleles on trait variance. We then assess the ability of RVATs to detect causal loci using simulations and human RNA-seq data.” “This has sometimes been interpreted to mean that rare variants make negligible contributions to complex trait heritability. Our work shows that RVATs are not robust to realistic human evolutionary forces, so general conclusions about the impact of rare variants on complex traits may be premature.”

Rare Variant Imputation

[PMID: 26450338] [Trends in Genetics]

Strategies for Imputing and Analyzing Rare Variants in Association Studies

“How do we best merge reference panels that may be on different sequencing technologies and have different coverage steps, and what is the impact of this on imputing rare variants? When analyzing rare variants, is the adjustment for ancestry enough? How do we best extend rare variant analysis methods, which have typically been focused on gene regions, to nongenic regions, where many GWAS hits have been found?”