SynthesisCommunications biology2024
Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9citing papers in PubMed
–field-weighted citation impact
What it found
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- Effects of remimazolam vs. propofol on plasma neurofilament light chain and postoperative delirium in frail elderly patients undergoing major non-cardiac surgery: a prospective, randomized, assessor-blinded controlled trial.BMC anesthesiology · 2026Trial
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Multi-omics integration and clinical validation identify CKAP2 as a diagnostic biomarker for bladder cancer.World journal of surgical oncology · 2026Article
- From Bench to Bedside: Neurofilament Light Chain as a Biomarker in Ischemic Stroke.Current medical science · 2026Review
- Sex-Related Differences in Circular RNA Expression in Multiple Sclerosis: A Pilot Study.Journal of molecular neuroscience : MN · 2026Article
- Brain and retina in Alzheimer's disease: Pathological intersections and estimates from imaging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults.Clinical epigenetics · 2025Article
- Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker.Brain communications · 2025Article
- Introducing neurofilament light chain measure in psychiatry: current evidence, opportunities, and pitfalls.Molecular psychiatry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors.
Shahzad Ahmad *Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.ORCID 0000-0002-8658-3790
Mohammad Aslam Imtiaz *Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1/99, 53127, Bonn, Germany.ORCID 0000-0003-2762-3227
Aniket MishraUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.ORCID 0000-0002-8141-1543
Ruiqi WangBoston University, Boston, MA, 02215, USA.
Marisol Herrera-RiveroDepartment of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.ORCID 0000-0001-7064-9487
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, 1730 Minor Ave #1360, Seattle, WA, 98101, USA.ORCID 0000-0002-3409-1110
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street Houston, Houston, 77030, TX, USA.ORCID 0000-0003-0677-8158
Gennady RoshchupkinDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.ORCID 0000-0002-3403-2313
Edith HoferClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.
Mark LogueNational Center for PTSD, Behavioral Sciences Division at VA Boston Healthcare System, Boston, 150 South Huntington Avenue, Boston, MA, 02130, USA.ORCID 0000-0001-9347-7892
W T LongstrethDepartments of Neurology and Epidemiology, University of Washington, Seattle, 3980 15th Ave NE Seattle, Seattle, WA, 98195, USA.
Rui XiaBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street Houston, Houston, 77030, TX, USA.
Vincent BouteloupUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
Thomas MosleyMIND Center, University of Mississippi Medical Center, Jackson, 2500 North State Street, Jackson, MS, 39216, USA.
Lenore J LaunerLaboratory of Epidemiology and Population Science, NIA Intramural Research Program, 251 Bayview Blvd, Baltimore, MD, 21224, USA.ORCID 0000-0002-3238-7612
Michael KhalilDepartment of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.ORCID 0000-0002-5350-3328
Jens KuhleResearch Center for Clinical Neuroimmunology and Neuroscience University Hospital, Spitalstrasse 2, CH-4031, Basel, Switzerland.
Robert A RissmanDepartment of Physiology and Neuroscience, Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, California, USA.
Genevieve CheneUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
Carole DufouilUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.ORCID 0000-0003-2442-4476
Luc DjousséBrigham and Women's Hospital, Harvard Medical School, Boston, 75 FRANCIS STREET, BOSTON MA 02115, MA, Boston, USA.
Michael J LyonsDepartment of Psychological & Brain Sciences, Boston University, Boston, 64 Cummington Mall # 149, Boston, MA, 02215, USA.
Kenneth J MukamalBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, 330 Brookline Avenue Boston, MA, 02215, USA.ORCID 0000-0001-8450-6970
William S KremenDepartment of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-8629-5609
Carol E FranzDepartment of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-8987-1755
Reinhold SchmidtClinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.
Stephanie DebetteUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.ORCID 0000-0001-8675-7968
Monique M B BretelerPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1/99, 53127, Bonn, Germany.ORCID 0000-0002-0626-9305
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Institut für Epidemiologie und Sozialmedizin Albert-Schweitzer-Campus 1, Gebäude D3 48149, Münster, Germany.
Qiong YangBoston University, Boston, MA, 02215, USA.ORCID 0000-0002-3658-1375
Sudha SeshadriBoston University, Boston, MA, 02215, USA.ORCID 0000-0001-6135-2622
N Ahmad AzizPopulation Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1/99, 53127, Bonn, Germany.ORCID 0000-0001-6184-458X
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.ORCID 0000-0002-9476-7143
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands. m.a.ikram@erasmusmc.nl.ORCID 0000-0003-0372-8585
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MThe VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)R01AG050595 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELMAN, JEREMY A, FRANZ, CAROL ELAINE · 2015 to 2024
$28.0MUSCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARTHUR W TOGA · 2020 to 2026
$27.8MSouth Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Sudha Seshadri · 2021 to 2026
$24.0MA Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MEPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4MTHE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7MTemporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham CohortsR01AG054076 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DECARLI, CHARLES, SESHADRI, SUDHA · 2016 to 2020
$12.3MNCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01 HG004729NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800003INHLBI NIH HHS HHSN268201800004INHLBI NIH HHS HHSN268201800005INHLBI NIH HHS HHSN268201800006INHLBI NIH HHS HHSN268201800007INHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC065226NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL093029NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS K01 AG063805NIA NIH HHS K24 AG046373NIA NIH HHS K24 AG065525NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG053325NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG076838NIA NIH HHS R03 AG065643NIA NIH HHS RF1 AG059421NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NIDDK NIH HHS P30 DK063491NINDS NIH HHS UF1 NS125513NINDS NIH HHS UH3 NS100605
Abstract
Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aβ-40, Aβ-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.
Indexed as
Genome-Wide Association StudyNeurodegenerative DiseasesNeurofilament ProteinsAlzheimer DiseaseBiomarkersFemaleGenetic LociGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotideBiomarkersneurofilament protein LNeurofilament Proteins
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