Enrichment of Rare and Uncommon Neanderthal Polymorphisms in Autistic Probands and Siblings

Abstract

Homo sapiensand 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 genic Neanderthal single nucleotide polymorphisms (SNP) may be playing in autism susceptibility using data from the Simons Foundation Powering Autism Research (SPARK) and Genotype-Tissue Expression (GTEx) databases. We have discovered that rare and uncommon variants are significantly enriched in both European- and African-American autistic probands and their unaffected siblings compared to race-matched controls. In addition, we have identified 51 SNPs (p51) significantly enriched in European-American cases of autism, 13 of which fall within autism-associated genes, as well as 1 SNP in African-American probands. In addition, SNPs within the p51 network display significant linkage disequilibrium with one another, indicating they may more often be co-inherited in autism. These results strongly suggest Neanderthal-derived DNA is playing a significant role in autism susceptibility across major populations in the United States.