Excess of rare, inherited truncating mutations in autism View Full Text


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Article Info

DATE

2015-05-11

AUTHORS

Niklas Krumm, Tychele N. Turner, Carl Baker, Laura Vives, Kiana Mohajeri, Kali Witherspoon, Archana Raja, Bradley P. Coe, Holly A. Stessman, Zong-Xiao He, Suzanne M. Leal, Raphael Bernier, Evan E. Eichler

ABSTRACT

To assess the relative impact of inherited and de novo variants on autism risk, we generated a comprehensive set of exonic single-nucleotide variants (SNVs) and copy number variants (CNVs) from 2,377 families with autism. We find that private, inherited truncating SNVs in conserved genes are enriched in probands (odds ratio = 1.14, P = 0.0002) in comparison to unaffected siblings, an effect involving significant maternal transmission bias to sons. We also observe a bias for inherited CNVs, specifically for small (<100 kb), maternally inherited events (P = 0.01) that are enriched in CHD8 target genes (P = 7.4 × 10(-3)). Using a logistic regression model, we show that private truncating SNVs and rare, inherited CNVs are statistically independent risk factors for autism, with odds ratios of 1.11 (P = 0.0002) and 1.23 (P = 0.01), respectively. This analysis identifies a second class of candidate genes (for example, RIMS1, CUL7 and LZTR1) where transmitted mutations may create a sensitized background but are unlikely to be completely penetrant. More... »

PAGES

582-588

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3303

    DOI

    http://dx.doi.org/10.1038/ng.3303

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1029270993

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25961944


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