Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings

Rini Pauly; Layla Johnson; F Alex Feltus; Emily L Casanova

doi:10.1038/s41380-024-02593-7

Enrichment of a subset of Neanderthal polymorphisms in autistic probands and siblings

Mol Psychiatry. 2024 May 17. doi: 10.1038/s41380-024-02593-7. Online ahead of print.

Authors

Rini Pauly¹, Layla Johnson², F Alex Feltus^{1

3

4}, Emily L Casanova⁵

Affiliations

¹ Biomedical Data Science and Informatics Program, Clemson University, Clemson, SC, 29634, USA.
² Department of Psychology, Loyola University, New Orleans, New Orleans, LA, 70118, USA.
³ Department of Genetics and Biochemistry, Clemson University, Clemson, SC, 29634, USA.
⁴ Center for Human Genetics, Clemson University, Clemson, SC, 29634, USA.
⁵ Department of Psychology, Loyola University, New Orleans, New Orleans, LA, 70118, USA. elcasano@loyno.edu.

PMID: 38760502
DOI: 10.1038/s41380-024-02593-7

Abstract

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.