Evidence map›Paper›PMID 35599344›Full record

SynthesisAnnals of neurology2022

Polygenic Resilience Modulates the Penetrance of Parkinson Disease Genetic Risk Factors.

Hui Liu, Mohammad Dehestani, Cornelis Blauwendraat, Mary B Makarious, Hampton Leonard, Jonggeol J Kim, Claudia Schulte, Alastair Noyce, Benjamin M Jacobs, Isabelle Foote and 6 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Parkinson's Disease is Predominantly a Genetic Disease.Journal of Parkinson's disease · 2024
    Review
  7. Review
  8. Review
  9. Review
  10. Review
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 at 4 institutions in 3 countries.

Hui LiuDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases, Tübingen, Germany.ORCID 0000-0001-5308-0874
Mohammad DehestaniDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases, Tübingen, Germany.
Cornelis BlauwendraatLaboratory of Neurogenetics, Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9358-8111
Mary B MakariousLaboratory of Neurogenetics, Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Hampton LeonardData Tecnica International, Glen Echo, MD, USA.
Jonggeol J KimLaboratory of Neurogenetics, Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Claudia SchulteDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases, Tübingen, Germany.
Alastair NoycePreventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.ORCID 0000-0003-3027-5497
Benjamin M JacobsPreventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
Isabelle FootePreventive Neurology Unit, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.ORCID 0000-0002-0253-4116
Manu SharmaDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases, Tübingen, Germany.ORCID 0000-0002-1260-5416
International Parkinson's Disease Genomics Consortium; Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease Consortium
Mike NallsCenter for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
Andrew SingletonLaboratory of Neurogenetics, Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Thomas GasserDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and German Center of Neurodegenerative Diseases, Tübingen, Germany.
Sara Bandres-CigaLaboratory of Neurogenetics, Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0056-1361
National Institutes of Health · USGerman Center for Neurodegenerative Diseases · DEQueen Mary University of London · GBData Tecnica International (United States) · US

Funding

Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
MIDCAREER AWARD IN PATIENT ORIENTED RESEARCH ON AGINGK24AG000949 · NIA · YALE UNIVERSITY · PI INOUYE, SHARON K. · 1999 to 2009
$1.4M
Intramural NIH HHS Z01 AG000949Intramural NIH HHS Z99 AG999999Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/V028766/1NIA NIH HHS K24 AG000949
6 · The paper itself

Abstract

objectiveThe aim of the current study is to understand why some individuals avoid developing Parkinson disease (PD) despite being at relatively high genetic risk, using the largest datasets of individual-level genetic data available.

methodsWe calculated polygenic risk score to identify controls and matched PD cases with the highest burden of genetic risk for PD in the discovery cohort (International Parkinson's Disease Genomics Consortium, 7,204 PD cases and 9,412 controls) and validation cohorts (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease, 8,968 cases and 7,598 controls; UK Biobank, 2,639 PD cases and 14,301 controls; Accelerating Medicines Partnership-Parkinson's Disease Initiative, 2,248 cases and 2,817 controls). A genome-wide association study meta-analysis was performed on these individuals to understand genetic variation associated with resistance to disease. We further constructed a polygenic resilience score, and performed multimarker analysis of genomic annotation (MAGMA) gene-based analyses and functional enrichment analyses.

resultsA higher polygenic resilience score was associated with a lower risk for PD (β = -0.054, standard error [SE] = 0.022, p = 0.013). Although no single locus reached genome-wide significance, MAGMA gene-based analyses nominated TBCA as a putative gene. Furthermore, we estimated the narrow-sense heritability associated with resilience to PD (h

interpretationThe present study represents a novel and comprehensive assessment of heritable genetic variation contributing to PD resistance. We show that a genetic resilience score can modify the penetrance of PD genetic risk factors and therefore protect individuals carrying a high-risk genetic burden from developing PD. ANN NEUROL 2022;92:270-278.

Indexed as

Parkinson DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPenetrancePolymorphism, Single NucleotideRisk Factors

Identifiers

PMID35599344
PMCPMC9329258
OpenAlexW4281291604

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.