Expressive

rs1065712 - CTSB

Magnitude 2.0 · 4 studies on file

Reported associations

  • New insights into the genetic etiology of Alzheimer's disease and related dementias - Unknown journal (n.d.) · Unknown authors · PubMed 35379992

    ABSTRACT: Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score ass

  • Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease - Unknown journal (n.d.) · Unknown authors · PubMed 37198259

    ABSTRACT: Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity

  • Mapping the proteo-genomic convergence of human diseases - Unknown journal (n.d.) · Unknown authors · PubMed 34648354

    ABSTRACT: Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3,892 plasma proteins to create a cis-anchored gene-protein-disease map of 1,859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to 1) connect etiologically related diseases, 2) provide biological context for new or emerging disorders, and 3) integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at GWAS loci, addressing a major barrie

  • The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease - Unknown journal (n.d.) · Unknown authors · PubMed 37985413

    ABSTRACT: Abstract INTRODUCTION Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta‐analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome‐wide significant signal (odds ratio  = 2.93 [2.37-3.63], P = 2.6 × 10−23). The meta‐analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loc

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