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A Neanderthal Origin of Genetic Variants Associated with Asthma

Day, A. S. H.; Gaulton, K. J.

2023-11-02 genetics
10.1101/2023.10.30.564624 bioRxiv
Show abstract

While genome-wide association studies have implicated a number asthma-associated genes, whether the disease-linked variants originate from ancient genomes has not been explored. Here we show that of the 51 asthma-associated loci that we surveyed, 39 carry variants that were derived in the Neanderthal lineage. The shared sequences suggest that some asthma variants may have originated from the Neanderthal genome after admixture and subsequent introgression into the Eurasian population. Of note, one variant, rs4742170, previously linked to asthma and childhood wheezing, was shown in a recent study to disrupt glucocorticoid receptor binding to a putative IL33 enhancer, and elevate enhancer activity of this key asthma gene. Further analysis of the IL33-associated variant in publicly available single nucleus ATACseq data of the human lung addressed its localization in open chromatin, providing an additional approach to screen for variants that may impact the expression of asthma-associated genes. Together, these findings suggest a possible Neanderthal origin of genetic variants associated with asthma.

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