Wroten Mathew, Yoon Seungtai, Andrews Peter, Yamrom Boris, Ronemus Michael, Buja Andreas, Krieger Abba M, Levy Dan, Ye Kenny, Wigler Michael, Iossifov Ivan
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Department of Statistics and Data Science, the Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
Cell Genom. 2023 May 8;3(6):100319. doi: 10.1016/j.xgen.2023.100319. eCollection 2023 Jun 14.
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.
在对数千个家庭进行研究时，我们发现，患自闭症的同胞比随机预期的情况共享了更多的父母基因组，而未患自闭症的同胞共享的则较少，这与遗传传递在自闭症发病率中的作用相符。父亲基因的额外共享非常显著（p值为0.0014），母亲基因的共享则不太显著（p值为0.31）。为了比较父母基因的共享情况，我们对减数分裂重组的差异进行了调整，得出他们平等共享的p值为0.15。这些观察结果与某些认为母亲携带的致病因素比父亲更多的模型相悖。尽管如此，我们提出的模型表明，即便母亲携带的致病因素更多，依然能观察到父亲基因的更多共享。更普遍地说，我们对基因共享的观察建立了任何完整的自闭症遗传模型都必须满足的定量限制，并且我们的方法可能适用于其他复杂疾病。
