Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 66,889 bioRxiv papers from 294,492 authors.

Inferring the molecular mechanisms of noncoding Alzheimer's disease-associated genetic variants

By Alexandre Amlie-Wolf, Mitchell Tang, Jessica Way, Beth Dombroski, Ming Jiang, Nicholas Vrettos, Yi-Fan Chou, Yi Zhao, Amanda Kuzma, Elisabeth E. Mlynarski, Yuk Yee Leung, Christopher D Brown, Li-San Wang, Gerard D. Schellenberg

Posted 27 Aug 2018
bioRxiv DOI: 10.1101/401471 (published DOI: 10.3233/JAD-190568)

INTRODUCTION: We set out to characterize the causal variants, regulatory mechanisms, tissue contexts, and target genes underlying noncoding late-onset Alzheimer's Disease (LOAD)-associated genetic signals. METHODS: We applied our INFERNO method to the IGAP genome-wide association study (GWAS) data, annotating all potentially causal variants with tissue-specific regulatory activity. Bayesian co-localization analysis of GWAS summary statistics and eQTL data was performed to identify tissue-specific target genes. RESULTS: INFERNO identified enhancer dysregulation in all 19 tag regions analyzed, significant enrichments of enhancer overlaps in the immune-related blood category, and co-localized eQTL signals overlapping enhancers from the matching tissue class in ten regions (ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, EPHA1, FERMT2, ZCWPW1). We validated the allele-specific effects of several variants on enhancer function using luciferase expression assays. DISCUSSION: Integrating functional genomics with GWAS signals yielded insights into the regulatory mechanisms, tissue contexts, and genes affected by noncoding genetic variation associated with LOAD risk.

Download data

  • Downloaded 525 times
  • Download rankings, all-time:
    • Site-wide: 19,726 out of 66,889
    • In bioinformatics: 2,909 out of 6,601
  • Year to date:
    • Site-wide: 18,892 out of 66,889
  • Since beginning of last month:
    • Site-wide: 26,999 out of 66,889

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News