New mutations, old statistical challenges

Based on targeted sequencing of 208 genes in 11,730 neurodevelopmental disorder cases, Stessman et al. report the identification of 91 genes associated (at a False Discovery Rate [FDR] of 0.1) with autism spectrum disorders (ASD), intellectual disability (ID), and developmental delay (DD)-including what they characterize as 38 novel genes, not previously reported as connected with these diseases. If true, this would represent a substantial step forward. Unfortunately, each of the two discovery analyses (1. De novo mutation analysis and, 2. a comparison of private mutations with public control data) contain critical statistical flaws. When one accounts for these problems, fewer than half of the genes - and very few, if any, of the novel findings - survive. These errors have implications for how future analyses should be conducted, for understanding the genetic basis of these disorders, and for genomic medicine.

• Publication year

  2017

• Venue

  bioRxiv

• Publication date

  2017-03-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/115964
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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