Friday, April 24, 2015

Paternal sperm in autism

"In summary, we have identified relatively large inter-individual differences in paternal sperm DNAm that associate with later 12-month ASD-related phenotype in their biological offspring, among a sample of autism enriched-risk infant siblings. Many of these regions of paternal sperm DNAm were also associated with ASD in cerebellum brain samples. Further, the genes implicated are enriched for neurodevelopment and include regions implicated in Prader-Willi syndrome. This unique set of biosamples is comparatively small, given the nature of the biosample type and required perinatal collection timing in an enriched-risk cohort. Thus it is important to examine these findings in larger samples to confirm these associations and explore mechanistic implications."

See:  Feinberg JI, Bakulski KM, Jaffe AE, Tryggvadottir R, Brown SC, Goldman LR,
Croen LA, Hertz-Picciotto I, Newschaffer CJ, Daniele Fallin M, Feinberg AP.
Paternal sperm DNA methylation associated with early signs of autism risk in an
autism-enriched cohort. Int J Epidemiol. 2015 Apr 14. pii: dyv028.

Father's Sperm Linked to Autism

1 comment:

  1. Abstract

    Krumm N, Turner TN, Baker C, Vives L, Mohajeri K, Witherspoon K, Raja A, Coe
    BP, Stessman HA, He ZX, Leal SM, Bernier R, Eichler EE. Excess of rare, inherited
    truncating mutations in autism. Nat Genet. 2015 May 11. doi: 10.1038/ng.3303.
    [Epub ahead of print]

    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.