Evidence map›Paper›PMID 40672290›Full record

ArticlebioRxiv : the preprint server for biology2025

Context-dependent regulatory variants in Alzheimer's disease.

Ziheng Chen, Yaxuan Liu, Ashley R Brown, Heather H Sestili, Easwaran Ramamurthy, Xushen Xiong, Dmitry Prokopenko, BaDoi N Phan, Lahari Gadey, Peinan Hu and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ziheng ChenDepartment of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0001-5709-8529
Yaxuan LiuComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0003-2359-5564
Ashley R BrownComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-3091-3930
Heather H SestiliComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-3944-3429
Easwaran RamamurthyComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-2439-0600
Xushen XiongBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-7090-7503
Dmitry ProkopenkoHarvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1844-5652
BaDoi N PhanComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0001-6331-5980
Lahari GadeyComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0003-0914-2104
Peinan HuDepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.ORCID 0000-0003-3229-1079
Li-Huei TsaiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0003-1262-0592
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.ORCID 0000-0002-0108-124X
Winston HideHarvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-8621-3271
Rudolph E TanziHarvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-7032-1454
Manolis KellisBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-7113-9630
Andreas R PfenningComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-3447-9801

Funding

Interpreting the regulatory mechanisms underlying the predisposition to substance use disordersDP1DA046585 · NIDA · CARNEGIE-MELLON UNIVERSITY · PI PFENNING, ANDREAS ROBERT · 2018 to 2022
$2.4M
Integrating primate-rodent cell types and epigenomics to identify conservation in substance addictionF30DA053020 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PHAN, BADOI NGUYEN · 2021 to 2024
$204k
NIDA NIH HHS DP1 DA046585NIDA NIH HHS F30 DA053020
6 · The paper itself

Abstract

Noncoding genetic variants underlie many complex diseases, yet identifying and interpreting their functional impacts remains challenging. Late-onset Alzheimer's disease (LOAD), a polygenic neurodegenerative disorder, exemplifies this challenge. The disease is strongly associated with noncoding variation, including common variants enriched in microglial enhancers and rare variants that are hypothesized to influence neurodevelopment and synaptic plasticity. These variants often perturb regulatory sequences by disrupting transcription factor (TF) motifs or altering local TF interactions, thereby reshaping gene expression and chromatin accessibility. However, assessing their impact is complicated by the context-dependent functions of regulatory sequences, underscoring the need to systematically examine variant effects across diverse tissues, cell types, and cellular states. Here, we combined

Identifiers

PMID40672290
PMCPMC12265656

What OpenQuestion holds

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LicenceCC BY-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.