Hyposmia (decreased smell function) is a common early symptom of Parkinson's disease (PD). The shared genetic architecture between hyposmia and PD is unknown. We leveraged genome-wide association study (GWAS) results for self-assessment of 'ability to smell' and PD diagnosis to determine shared genetic architecture between the two traits. Linkage disequilibrium score (LDSC) regression found that the sense of smell negatively correlated at a genome-wide level with PD. Local Analysis of [co]Variant Association (LAVA) found negative correlations in four genetic loci near GBA1, ANAPC4, SNCA, and MAPT, indicating shared genetic liability only within a subset of prominent PD risk genes. Using Mendelian randomization, we found evidence for a strong causal relationship between PD and liability towards poorer sense of smell, but weaker evidence for the reverse direction. This work highlights the heritability of olfactory function and its relationship with PD heritability and provides further insight into the association between PD and hyposmia.
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http://dx.doi.org/10.1038/s41531-024-00838-4 | DOI Listing |
Discov Oncol
January 2025
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.
View Article and Find Full Text PDFActa Neuropathol
January 2025
Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.
View Article and Find Full Text PDFMol Ecol
January 2025
Department of Environmental Toxicology, University of California Davis, Davis, California, USA.
Characterising patterns of genetic diversity including evidence of local adaptation is relevant for predicting and managing species recovering from overexploitation in the face of climate change. Red abalone (Haliotis rufescens) is a species of conservation concern due to recent declines from overharvesting, disease and climate change, resulting in the closure of commercial and recreational fisheries. Using whole-genome resequencing data from 23 populations spanning their entire range (southern Oregon, USA, to Baja California, MEX) we investigated patterns of population connectivity and genotype-environment associations that would reveal local adaptation across the mosaic of coastal environments that define the California Current System (CCS).
View Article and Find Full Text PDFHum Genomics
January 2025
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Richards Building B304, 3700 Hamilton Walk, Philadelphia, PA, 19104, USA.
Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.
View Article and Find Full Text PDFBreast Cancer Res
January 2025
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia.
Background: Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies.
Methods: This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity).
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