bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.08.10.607452

Co-localized SNPs Affecting the Expression of Taste Perception Genes are linked to Alzheimer's Disease

Joseph, P. V.·Abbas, M.·Goodney, G.·Diallo, A.·Gaye, A.
View original source ↗Export metadata ↓

Abstract

BackgroundWhile previous research has shown the potential links between taste perception pathways and brain-related conditions, the area involving Alzheimers disease remains incompletely understood. Taste perception involves neurotransmitter signaling, including serotonin, glutamate, and dopamine. Disruptions in these pathways are implicated in neurodegenerative diseases. The integration of olfactory and taste signals in flavor perception may impact brain health, evident in olfactory dysfunction as an early symptom in neurodegenerative conditions. Shared immune response and inflammatory pathways may contribute to the association between altered taste perception and conditions like neurodegeneration, present in Alzheimers disease. MethodsThis study consists of an exploration of expression-quantitative trait loci (eQTL), utilizing whole-blood transcriptome profiles, of 28 taste perception genes, from a combined cohort of 475 African American subjects. This comprehensive dataset was subsequently intersected with single-nucleotide polymorphisms (SNPs) identified in Genome-Wide Association Studies (GWAS) of Alzheimers Disease (AD). Finally, the investigation delved into assessing the association between eQTLs reported in GWAS of AD and the profiles of 741 proteins from the Olink Neurological Panel. ResultsThe eQTL analysis unveiled 3,547 statistically significant SNP-Gene associations, involving 412 distinct SNPs that spanned all 28 taste genes. In 17 GWAS studies encompassing various traits, a total of 14 SNPs associated with 12 genes were identified, with three SNPs consistently linked to Alzheimers disease across four GWAS studies. All three SNPs demonstrated significant associations with the down-regulation of TAS2R41, and two of them were additionally associated with the down-regulation of TAS2R60. In the subsequent pQTL analysis, two of the SNPs linked to TAS2R41 and TAS2R60 genes (rs117771145 and rs10228407) were correlated with the upregulation of two proteins, namely EPHB6 and ADGRB3. ConclusionsOur investigation introduces a new perspective to the understanding of Alzheimers disease, emphasizing the significance of bitter taste receptor genes in its pathogenesis. These discoveries set the stage for subsequent research to delve into these receptors as promising avenues for both intervention and diagnosis. Nevertheless, the translation of these genetic insights into clinical practice requires a more profound understanding of the implicated pathways and their pertinence to the diseases progression across diverse populations.

Source connections

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Joseph, P. V., Abbas, M., Goodney, G., Diallo, A., Gaye, A.. 2024-08-10. Co-localized SNPs Affecting the Expression of Taste Perception Genes are linked to Alzheimer's Disease. https://doi.org/10.1101/2024.08.10.607452

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Genomic correlates of metastatic competence and progression in human melanoma

Genomic events and their timing that grant a primary tumour the competence to disseminate remain poorly defined. We performed sequencing of 247 stage I/II primary cutaneous melanomas (CMs) and 60 matched metastases without intervening therapy from a prospectively followed registry cohort with a median followup of 92 months, integrating copy-number, mutational, protein and spatial-transcriptomic analyses. Relapse was not distinguished by oncogenic point mutations, which were largely shared between primaries and metastases, but by somatic copy-number alterations (SCNAs) and global chromosomal instability. We defined OncoCycle, a six-gene copy-number signature (amplification of CDK4, MCL1 and CD276; biallelic loss of CDKN2A, CDKN2B and TP53BP1) that predicted relapse independently of established clinicopathological features in melanoma, and a pan-cancer analysis. In matched pairs, metastatic progression was driven by continued copy-number evolution and reduction in intra-tumoural heterogeneity, rather than by acquired point mutations, and OncoCycle alterations from primary tumours were preserved in metastasis seeding clones. Clonal reconstruction revealed both monoclonal and polyclonal metastasis seeding, and spatial transcriptomics resolved copy-number-defined metastatic subclones occupying and programming distinct immune and stromal niches. Thus, metastatic competence was primed early by focal SCNAs on a background of chromosomal instability, elaborated by continued copy-number evolution during dissemination and spatio-temporal interactions with the tumour-microenvironment.

genomics↗
bioRxiv2026

Identifying, phasing, and structurally annotating sex chromosomes for genome assemblies using CBS-tools

A complete reference genome for species with chromosomally-determined separate sexes should contain scaffolds for all sex chromosome homologs. However, sex chromosomes present distinct computational challenges compared to autosomes. Here we present a k-mer based analysis that utilizes whole-genome sequencing of a few sex-identified isolates: Cytogenetics-By-Sequencing (CBS) tools. Unlike other approaches that typically address one aspect of the sex chromosomes, CBS-tools strives to guide users from the discovery of the heterogametic sex through identifying the sex-determination region (SDR). The core of CBS-tools is automated quantification of sex-specific k-mers in order to predict the heterogametic sex. Using publicly-available datasets, CBS-tools correctly identified the known sex-system of the 31 species tested. Additionally, we used these k-mers to verify and correct phasing of sex chromosomes between haplotypes in species representing different sex-systems. Finally, we used these k-mers to delimit the SDR boundary using an interactive web platform. CBS-tools was developed with previously unexplored sex chromosome systems in mind, but is also suitable for well-examined sex chromosome pairs.

genomics↗
bioRxiv2026

Evolutionary dynamics of the insertion sequence IS6110 in the Mycobacterium tuberculosis complex

Insertion sequences (IS) are the most common type of transposable element in prokaryotes and shape the structure of genomes through transposition and by providing a substrate for recombination. Despite the mutational impact of IS, the evolutionary dynamics of most elements in host species remain unknown. Here we study the dynamics of IS6110 in 10,000 strains of the Mycobacterium tuberculosis complex (MTBC). We developed a tool that allows the detection and comparison of IS insertions from short reads without using a reference genome. Using ancestral state reconstruction (ASR) on presence-absence patterns of IS6110, we describe the distribution of copy numbers (CNs) in the MTBC, infer birth rates of the element, and identify genomic regions with large numbers of parallel IS6110 insertions. Copy numbers in the MTBC range from 1 in some clades to more than 30 in strains of La3 (M. orygis). IS6110 birth rates scale approximately linearly with copy number and are elevated on terminal branches, consistent with the delayed action of purifying selection. A key characteristic of IS6110 is its occurrence in hotspots: the 5% most frequently targeted regions account for half of all independent insertion events. The motif 5'-TCTCAAAW-3' is enriched around target sites and in hotspots, suggesting that the accumulation of insertions in these regions results through a combination of non-random insertion and purifying selection in other regions. To conclude the study, we propose a niche constraints model according to which the distribution of IS6110 in the MTBC is governed by the rarity of regions that have both suitable DNA properties and little functional value for the host.

genomics↗