Sharing parental genomes by siblings concordant or discordant for autism

Mathew Wroten; Seungtai Yoon; Peter Andrews; Boris Yamrom; Michael Ronemus; Andreas Buja; Abba M Krieger; Dan Levy; Kenny Ye; Michael Wigler; Ivan Iossifov

doi:10.1016/j.xgen.2023.100319

Sharing parental genomes by siblings concordant or discordant for autism

Cell Genom. 2023 May 8;3(6):100319. doi: 10.1016/j.xgen.2023.100319. eCollection 2023 Jun 14.

Authors

Mathew Wroten¹, Seungtai Yoon¹, Peter Andrews¹, Boris Yamrom¹, Michael Ronemus¹, Andreas Buja^{2

3}, Abba M Krieger², Dan Levy¹, Kenny Ye⁴, Michael Wigler^{1

5}, Ivan Iossifov^{1

5}

Affiliations

¹ Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
² Department of Statistics and Data Science, the Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
³ Flatiron Institute, Simons Foundation, New York, NY, USA.
⁴ Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
⁵ New York Genome Center, New York, NY, USA.

Abstract

Studying thousands of families, we find siblings concordant for autism share more of their parental genomes than expected by chance, and discordant siblings share less, consistent with a role of transmission in autism incidence. The excess sharing of the father is highly significant (p value of 0.0014), with less significance for the mother (p value of 0.31). To compare parental sharing, we adjust for differences in meiotic recombination to obtain a p value of 0.15 that they are shared equally. These observations are contrary to certain models in which the mother carries a greater load than the father. Nevertheless, we present models in which greater sharing of the father is observed even though the mother carries a greater load. More generally, our observations of sharing establish quantitative constraints that any complete genetic model of autism must satisfy, and our methods may be applicable to other complex disorders.

Keywords: autism; discretized sharing; genetic models of autism; parental genomic sharing.