Excess of rare, inherited truncating mutations in autism  

Oleh:

Krumm, Niklas ; Turner, Tychele N ; Baker, Carl ; Vives, Laura ; Mohajeri, Kiana

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 47 no. 06 (Jun. 2015), page 582–588.

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Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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