Insufficient Evidence for “Autism-Specific” Genes

作者：Scott M. Myers, Thomas D. Challman, Raphael Bernier, Thomas Bourgeron, Wendy K. Chung, John N. Constantino, Evan E. Eichler, Sébastien Jacquemont, David T. Miller, Kevin J. Mitchell, Huda Y. Zoghbi, Christa Lese Martin, David H. Ledbetter · 发表于：The American Journal of Human Genetics · 年份：2020 · DOI：10.1016/j.ajhg.2020.04.004 · 被引用次数：170 · 研究领域：Autism Spectrum Disorder Research、Genetics and Neurodevelopmental Disorders、Genomics and Rare Diseases

Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively "autism-specific" genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research. We argue that there is currently insufficient evidence to establish meaningful ASD specificity of any genes based on large-effect rare-variant data.