Biomedical Data Science and Informatics Program, Clemson University, Clemson, SC, 29634, USA.
Department of Psychology, Loyola University, New Orleans, New Orleans, LA, 70118, USA.
Mol Psychiatry. 2024 Nov;29(11):3452-3461. doi: 10.1038/s41380-024-02593-7. Epub 2024 May 17.
Homo sapiens and Neanderthals underwent hybridization during the Middle/Upper Paleolithic age, culminating in retention of small amounts of Neanderthal-derived DNA in the modern human genome. In the current study, we address the potential roles Neanderthal single nucleotide polymorphisms (SNP) may be playing in autism susceptibility in samples of black non-Hispanic, white Hispanic, and white non-Hispanic people using data from the Simons Foundation Powering Autism Research (SPARK), Genotype-Tissue Expression (GTEx), and 1000 Genomes (1000G) databases. We have discovered that rare variants are significantly enriched in autistic probands compared to race-matched controls. In addition, we have identified 25 rare and common SNPs that are significantly enriched in autism on different ethnic backgrounds, some of which show significant clinical associations. We have also identified other SNPs that share more specific genotype-phenotype correlations but which are not necessarily enriched in autism and yet may nevertheless play roles in comorbid phenotype expression (e.g., intellectual disability, epilepsy, and language regression). These results strongly suggest Neanderthal-derived DNA is playing a significant role in autism susceptibility across major populations in the United States.
智人和尼安德特人在中更新世/上新世时期发生了杂交，最终导致现代人类基因组中保留了少量尼安德特人衍生的 DNA。在当前的研究中，我们利用来自西蒙斯基金会自闭症研究动力（SPARK）、基因-组织表达（GTEx）和 1000 基因组（1000G）数据库的数据，研究了尼安德特人单核苷酸多态性（SNP）在黑非西班牙裔、白西班牙裔和白非西班牙裔人群的自闭症易感性中可能发挥的潜在作用。我们发现，与种族匹配的对照组相比，罕见变异在自闭症患者中明显富集。此外，我们还确定了 25 个在不同种族背景下与自闭症显著富集的罕见和常见 SNPs，其中一些表现出显著的临床相关性。我们还发现了其他共享更具体基因型-表型相关性的 SNPs，但它们不一定在自闭症中富集，但可能在共病表型表达（如智力障碍、癫痫和语言退化）中发挥作用。这些结果强烈表明，尼安德特人衍生的 DNA 在包括美国在内的主要人群的自闭症易感性中发挥着重要作用。
