Evidence map›Paper›PMID 38496508›Full record

ArticlebioRxiv : the preprint server for biology2024

Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies.

Sumaiya Nazeen, Xinyuan Wang, Dina Zielinski, Isabel Lam, Erinc Hallacli, Ping Xu, Elizabeth Ethier, Ronya Strom, Camila A Zanella, Vanitha Nithianandam and 29 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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, 3 citations in OpenAlex.

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

39 authors at 10 institutions in 2 countries.

Sumaiya NazeenDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6313-6357
Xinyuan WangDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3107-8359
Dina ZielinskiDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Isabel LamDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6247-8080
Erinc HallacliDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ping XuDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth EthierDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ronya StromDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Camila A ZanellaDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Vanitha NithianandamDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Dylan RitterThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Alexander HendersonThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Nathalie SauratThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Jalwa AfrozThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Andrew Nutter-UphamWhitehead Institute of Biomedical Research, Cambridge, MA, USA.
Hadar BenyaminiWhitehead Institute of Biomedical Research, Cambridge, MA, USA.
Joseph CoptyGarvan Institute of Medical Research, Sydney, NSW, Australia.
Shyamsundar RavishankarGarvan Institute of Medical Research, Sydney, NSW, Australia.
Autumn MorrowDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jonathan MitchelDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Drew NeavinGarvan Institute of Medical Research, Sydney, NSW, Australia.
Renuka GuptaGarvan Institute of Medical Research, Sydney, NSW, Australia.
Nona FarbehiGarvan Institute of Medical Research, Sydney, NSW, Australia.
Jennifer GrundmanDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Richard H MyersDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Clemens R ScherzerDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
Vivianna M Van DeerlinCenter for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
Antony A CooperGarvan Institute of Medical Research, Sydney, NSW, Australia.
Edward B LeeCenter for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
Yaniv ErlichDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Susan LindquistDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jian PengDepartment of Computer Science, University of Illinois Urbana-Champaign, Champaign, IL, USA.
Daniel H GeschwindCenter for Autism Research and Treatment, Semel Institute, Program in Neurogenetics, Department of Neurology and Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Joseph PowellGarvan Institute of Medical Research, Sydney, NSW, Australia.
Lorenz StuderThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.ORCID 0000-0003-0741-7987
Mel B FeanyDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Shamil R SunyaevDivision of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5715-5677
Vikram KhuranaDivision of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4018-5527
Brigham and Women's Hospital · USGarvan Institute of Medical Research · AUKettering University · USInstitute for Neurodegenerative Disorders · USBroad Institute · USUniversity of California, Los Angeles · USWhitehead Institute for Biomedical Research · USBoston University · USHarvard University · USUniversity of Illinois Urbana-Champaign · US

Funding

Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
The origin, the function and the phenotypic impact of human allelesR35GM127131 · NIGMS · HARVARD MEDICAL SCHOOL · PI SHAMIL SUNYAEV · 2018 to 2026
$8.1M
Elucidating the Biological Differences Between Distinct Fibrillar and Non-Fibrillar Alpha-Synuclein Inclusions in Human Stem-Cell ModelsR01NS109209 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KHURANA, VIKRAM · 2020 to 2024
$4.5M
Genetic Analysis of NeurodegenerationR35NS132225 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI MEL B FEANY · 2023 to 2026
$3.7M
NIA NIH HHS T32 AG000222NIGMS NIH HHS R35 GM127131NINDS NIH HHS R01 NS109209NINDS NIH HHS R35 NS132225
6 · The paper itself

Abstract

Whether neurodegenerative diseases linked to misfolding of the same protein share genetic risk drivers or whether different protein-aggregation pathologies in neurodegeneration are mechanistically related remains uncertain. Conventional genetic analyses are underpowered to address these questions. Through careful selection of patients based on protein aggregation phenotype (rather than clinical diagnosis) we can increase statistical power to detect associated variants in a targeted set of genes that modify proteotoxicities. Genetic modifiers of alpha-synuclein (ɑS) and beta-amyloid (Aβ) cytotoxicity in yeast are enriched in risk factors for Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. Here, along with known AD/PD risk genes, we deeply sequenced exomes of 430 ɑS/Aβ modifier genes in patients across alpha-synucleinopathies (PD, Lewy body dementia and multiple system atrophy). Beyond known PD genes

Identifiers

PMID38496508
PMCPMC10942362
OpenAlexW4392449058

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.