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bioRxiv · 10.1101/103218

Calculating the statistical significance of rare variants causal for Mendelian and complex disorders

Rao, A. R.·Nelson, S. F.
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Abstract

With the expanding use of next-gen sequencing (NGS) to diagnose the thousands of rare Mendelian genetic diseases, it is critical to be able to interpret individual DNA variation. We developed a general method to better interpret the likelihood that a rare variant is disease causing if observed in a given gene or genic region mapping to a described protein domain, using genome-wide information from a large control sample. We implemented these methods as a web tool and demonstrate application to 19 relevant but diverse next-gen sequencing studies. Additionally, we calculate the statistical significance of findings involving multi-family studies with rare Mendelian disease and studies of large-scale complex disorders such as autism spectrum disorder.

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Rao, A. R., Nelson, S. F.. 2017-01-25. Calculating the statistical significance of rare variants causal for Mendelian and complex disorders. https://doi.org/10.1101/103218

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