Evidence map›Paper›PMID 42330948›Full record

ArticleCell genomics2026

NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease.

Sumaiya Nazeen, Xinyuan Wang, Autumn R Morrow, Ronya Strom, Elizabeth Ethier, Dylan Ritter, Alexander B H Henderson, Jalwa Afroz, Christopher S Cassa, Nathan O Stitziel and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Sumaiya NazeenDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; American Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Xinyuan WangAmerican Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Autumn R MorrowDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; American Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Ronya StromAmerican Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth EthierAmerican Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, 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 B H HendersonDepartment of Neurology, Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jalwa AfrozThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.
Christopher S CassaDivision of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nathan O StitzielCardiovascular Division, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Rajat M GuptaDivision of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Kelvin C LukDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Lorenz StuderThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA.
Vikram KhuranaAmerican Parkinson's Disease Association Center for Advanced Research, Harvard Biomarkers Study 2.0 and MyTrial Programs, Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA; Harvard Stem Cell Institute, Cambridge, MA, USA. Electronic address: khuranalab_admin@bwh.harvard.edu.
Shamil R SunyaevDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: ssunyaev@hms.harvard.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
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
Statistical methods for studies of rare variantsR01MH101244 · NIMH · HARVARD MEDICAL SCHOOL · PI Benjamin Michael Neale, ALKES L PRICE · 2013 to 2026
$9.4M
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
Predicting the impact of genetic variants, genes and pathways on human DiseaseU01HG012009 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ALKES L PRICE, Soumya Raychaudhuri · 2021 to 2026
$4.2M
NCI NIH HHS P30 CA008748NHGRI NIH HHS U01 HG012009NIA NIH HHS T32 AG000222NIGMS NIH HHS R35 GM127131NIMH NIH HHS R01 MH101244NINDS NIH HHS R01 NS109209
6 · The paper itself

Abstract

Studying the genetic basis of human phenotypes involves two primary strategies. Model-system experiments generate interpretable gene networks but do not establish relevance to human disease. In contrast, statistical genetics identifies variant- and gene-level associations but cannot test mechanistic models. Here, we bridge these approaches by introducing NERINE, a hierarchical model-based rare variant association test that incorporates gene network topology while remaining robust to network inaccuracies. NERINE supports analysis of networks from established pathway databases and model-system screens. A comprehensive search across pathway databases reveals associations for breast cancer, cardiovascular diseases, and type 2 diabetes not detected by single-gene tests. Applied to experimental screen-derived networks in Parkinson's disease (PD), NERINE highlights autophagy-, vesicle-trafficking-, and protein-homeostasis-related gene modules. Genome-scale CRISPR interference (CRISPRi) screening in human neurons and NERINE converge on PRL, revealing an intraneuronal α-synuclein/prolactin stress response that may impact resilience to PD.

Indexed as

alpha-SynucleinGene Regulatory NetworksParkinson DiseaseFemaleHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Phenotypealpha-SynucleinLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanSNCA protein, humanbreast cancercomplex disease geneticscoronary artery diseasemultivariate statistical geneticsmyocardial infarctionnetwork-based rare variant associationneuronal Parkinson's modelParkinson's diseasetype 2 diabetesα-synuclein/prolactin stress response

Identifiers

PMID42330948
PMCPMC13347950

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Registered trials

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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.