SynthesisStroke2018
Exome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Stroke, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 3 pooled it
1.1field-weighted citation impact, top 22% of its field
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.
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.
Who cites it
17 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Meta-analyses of genome-wide association studies identify novel loci influencing Japanese white matter hyperintensities.Journal of human genetics · 2026Pooled it
- Identification and validation of supervariants reveal novel loci associated with human white matter microstructure.Genome research · 2024Pooled it
- Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.Stroke · 2020Pooled it
- Genetic Architecture of Cerebral White Matter Hyperintensities in Diverse Hispanic/Latino Adults.Neurology. Genetics · 2025Article
- Integrating Genetic and Single-Cell Genomic Data to Reveal Brain Cell-Specific Regulation of Attention-Deficit/Hyperactivity Disorder Risk in the Prefrontal Cortex.Brain and behavior · 2025Article
- WMH Contributions to Cognitive Impairment: Rationale and Design of the Diverse VCID Study.Stroke · 2025Review
- The Magic and Mystery of TRIM65 in Diseases.Current medicinal chemistry · 2025Review
- Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities.Journal of stroke · 2024Review
- Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer's Disease: Results from the HELIAD Study.Current issues in molecular biology · 2024Article
- Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.Brain : a journal of neurology · 2023Article
- Genetic considerations in cerebral small vessel diseases.Frontiers in neurology · 2023Review
- Genetics of common cerebral small vessel disease.Nature reviews. Neurology · 2022Review
- Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities.Brain : a journal of neurology · 2021Article
- Gene-Environment Interactions for Cardiovascular Disease.Current atherosclerosis reports · 2021Review
- Identification of 20 novel loci associated with ischaemic stroke. Epigenome-wide association study.Epigenetics · 2020Article
- Genetics of Cerebral Small Vessel Disease.Stroke · 2020Review
- Genome-wide association study of cerebral small vessel disease reveals established and novel loci.Brain : a journal of neurology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
79 authors at 20 institutions in 10 countries.
Xueqiu JianFrom the Institute of Molecular Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (M.F., X.J.).
Claudia L SatizabalDepartment of Neurology, Boston University School of Medicine, MA (C.L.S., S. Seshadri).
Albert V SmithIcelandic Heart Association, Kópavogur, Iceland (A.V.S., G.E., S. Sigurdsson, V.G.G.).
Katharina WittfeldGerman Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Germany (K.W.).
Joshua C BisCardiovascular Health Research Unit (B.M.P., J.C.B., S.R.H.).
Jennifer A SmithDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (J.A.S., S.L.R.K., W.Z.).
Fang-Chi HsuDivision of Public Health Sciences (F.-C.H., J.D.).
Kwangsik NhoCenter for Neuroimaging, Indiana University School of Medicine, Indianapolis (K.N., S.L.R.).
Edith HoferDepartment of Neurology (E.H., R.S.).
Saskia P HagenaarsCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Paul A NyquistDepartment of Neurology and Neurosurgery (P.A.N., R.F.G.).
Aniket MishraBordeaux Population Health Research Centre U1219, Inserm, France (A.M., G.C., S.D.).
Hieab H H AdamsDepartment of Epidemiology (C.M.v.D., H.H.H.A.).
Shuo LiDepartment of Biostatistics, Boston University School of Public Health, MA (A.S.B., A.L.D., Q.Y., S.L.).
Alexander TeumerInstitute for Community Medicine (A.T.).
Wei ZhaoDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (J.A.S., S.L.R.K., W.Z.).
Barry I FreedmanDepartment of Internal Medicine (B.I.F.).
Yasaman SabaInstitute of Molecular Biology and Biochemistry (H.S., Y.S.), Medical University of Graz, Austria.
Lisa R YanekDepartment of Medicine (D.M.B., L.R.Y., R.A.M.), Johns Hopkins School of Medicine, Baltimore, MD.
Ganesh ChauhanBordeaux Population Health Research Centre U1219, Inserm, France (A.M., G.C., S.D.).
Mark A van BuchemDepartment of Radiology, Leiden University Medical Center, the Netherlands (M.A.v.B.).
Mary CushmanDepartment of Medicine, The University of Vermont Larner College of Medicine, Burlington (M.C.).
Natalie A RoyleCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
R Nick BryanDepartment of Diagnostic Medicine, Dell Medical School at The University of Texas at Austin (R.N.B.).
Wiro J NiessenDepartments of Radiology and Medical Informatics (W.J.N.).
Beverly G Windham
Anita L DeStefanoDepartment of Biostatistics, Boston University School of Public Health, MA (A.S.B., A.L.D., Q.Y., S.L.).
Mohamad HabesDepartment of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia (M.H.).
Susan R HeckbertCardiovascular Health Research Unit (B.M.P., J.C.B., S.R.H.).
Nicholette D PalmerDepartment of Biochemistry (D.W.B., N.D.P.), Wake Forest School of Medicine, Winston-Salem, NC.
Cora E LewisDepartment of Epidemiology, The University of Alabama at Birmingham School of Public Health (C.E.L.).
Gudny EiriksdottirIcelandic Heart Association, Kópavogur, Iceland (A.V.S., G.E., S. Sigurdsson, V.G.G.).
Pauline MaillardDepartment of Neurology, UC Davis School of Medicine (C.S.D., P.M.), CA.
Rasika A MathiasDepartment of Medicine (D.M.B., L.R.Y., R.A.M.), Johns Hopkins School of Medicine, Baltimore, MD.
Georg HomuthInstitute of Genetics and Functional Genomics, University of Greifswald, Germany (G.H.).
Maria Del C Valdés-HernándezCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Jasmin DiversDivision of Public Health Sciences (F.-C.H., J.D.).
Alexa S BeiserDepartment of Biostatistics, Boston University School of Public Health, MA (A.S.B., A.L.D., Q.Y., S.L.).
Sönke LangnerInstitute for Diagnostic Radiology and Neuroradiology (S.L.).
Kenneth M RiceDepartment of Biostatistics, University of Washington School of Public Health, Seattle (K.M.R.).
Mark E BastinCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, MA (A.S.B., A.L.D., Q.Y., S.L.).
Joseph A MaldjianDepartment of Radiology, The University of Texas Southwestern Medical Center, Dallas (J.A.M.).
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Stephen SidneyDivision of Research, Kaiser Permanente Northern California, Oakland (S. Sidney).
Shannon L RisacherCenter for Neuroimaging, Indiana University School of Medicine, Indianapolis (K.N., S.L.R.).
André G UitterlindenDepartments of Internal Medicine, Epidemiology, and Clinical Chemistry (A.G.U.).
Vilmundur G GudnasonIcelandic Heart Association, Kópavogur, Iceland (A.V.S., G.E., S. Sigurdsson, V.G.G.).
Matthias NauckInstitute for Clinical Chemistry and Laboratory Medicine (M.N.).
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Harbor-UCLA Medical Center, Torrance, CA (J.I.R.).
Pamela J SchreinerDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (P.J.S.).
Eric BoerwinkleHuman Genetics Center, The University of Texas Health Science Center at Houston School of Public Health (E.B.).
Cornelia M van DuijnDepartment of Epidemiology (C.M.v.D., H.H.H.A.).
Bernard MazoyerNeurodegeneratives Diseases Institute-CNRS UMR 5293 (B.M.), University of Bordeaux, France.
Bettina von SarnowskiDepartment of Neurology (B.v.S.).
Rebecca F GottesmanDepartment of Neurology and Neurosurgery (P.A.N., R.F.G.).
Daniel LevyPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (D.L.).
Sigurdur SigurdssonIcelandic Heart Association, Kópavogur, Iceland (A.V.S., G.E., S. Sigurdsson, V.G.G.).
Meike W VernooijDepartments of Radiology and Epidemiology (M.W.V.).
Stephen T TurnerDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (S.T.T.).
Reinhold SchmidtDepartment of Neurology (E.H., R.S.).
Joanna M WardlawCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Bruce M PsatyCardiovascular Health Research Unit (B.M.P., J.C.B., S.R.H.).
Thomas H Mosley
Charles S DeCarliDepartment of Neurology, UC Davis School of Medicine (C.S.D., P.M.), CA.
Andrew J Saykin
Donald W BowdenDepartment of Biochemistry (D.W.B., N.D.P.), Wake Forest School of Medicine, Winston-Salem, NC.
Diane M BeckerDepartment of Medicine (D.M.B., L.R.Y., R.A.M.), Johns Hopkins School of Medicine, Baltimore, MD.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, United Kingdom (I.J.D., J.M.W., J.M.S., M.d.C.V.-H., M.E.B., N.A.R., S.P.H.).
Helena SchmidtInstitute of Molecular Biology and Biochemistry (H.S., Y.S.), Medical University of Graz, Austria.
Sharon L R KardiaDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor (J.A.S., S.L.R.K., W.Z.).
M Arfan IkramDepartments of Epidemiology, Radiology and Neurology (M.A.I.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Stéphanie DebetteBordeaux Population Health Research Centre U1219, Inserm, France (A.M., G.C., S.D.).
Hans J GrabeDepartment of Psychiatry and Psychotherapy (H.J.G.), University Medicine Greifswald, Germany.
W T LongstrethDepartments of Neurology and Epidemiology (W.T.L.), University of Washington, Seattle, WA.
Sudha SeshadriDepartment of Neurology, Boston University School of Medicine, MA (C.L.S., S. Seshadri).
Lenore J LaunerLaboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, MD (L.J.L.).
Myriam FornageFrom the Institute of Molecular Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston (M.F., X.J.).
neuroCHARGE Working Group
University of Edinburgh · GBBoston University · USIcelandic Heart Association · ISCardiovascular Research Center · BRJohns Hopkins University · USThe University of Texas Health Science Center at Houston · USUniversity of Michigan–Ann Arbor · USBordeaux Population Health · FRFaculty of Public Health · GBMedical University of Graz · ATUnited States Nuclear Regulatory Commission · USUniversity of California, Davis · USUniversity of Washington · USWake Forest University · USBeverly Hospital · USDentsply Sirona (Sweden) · SEErasmus MC · NLGerman Center for Neurodegenerative Diseases · DEIndiana University – Purdue University Indianapolis · USIndiana University School of Medicine
Funding
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3MPRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9MTemporal 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
$12.3MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MARIC Neurocognitive Study (ARIC-NCS) Renewal UNC 4 of 5U01HL096899 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID J · 2010 to 2018
$7.5MARIC Neurocognitive Study (ARIC-NCS)U01HL096902 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2010 to 2018
$7.4MCHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MA Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1MCollaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4MSequence-based Discovery of AD Risk & Protective AllelesU01AG049506 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A., SALERNO, WILLIAM JAMES · 2014 to 2017
$3.8MCHARGE: Identifying Risk & Protective SNV for AD in ADSP Case-control SampleU01AG049505 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2014 to 2017
$3.0MMedical Research Council G0701120Medical Research Council MR/K026992/1Medical Research Council MR/M013111/1NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL119443NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114NIA NIH HHS P30 AG010129NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG054076NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG052409NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS087541NLM NIH HHS R01 LM012535
Abstract
Background and Purpose- White matter hyperintensities (WMH) on brain magnetic resonance imaging are typical signs of cerebral small vessel disease and may indicate various preclinical, age-related neurological disorders, such as stroke. Though WMH are highly heritable, known common variants explain a small proportion of the WMH variance. The contribution of low-frequency/rare coding variants to WMH burden has not been explored. Methods- In the discovery sample we recruited 20 719 stroke/dementia-free adults from 13 population-based cohort studies within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, among which 17 790 were of European ancestry and 2929 of African ancestry. We genotyped these participants at ≈250 000 mostly exonic variants with Illumina HumanExome BeadChip arrays. We performed ethnicity-specific linear regression on rank-normalized WMH in each study separately, which were then combined in meta-analyses to test for association with single variants and genes aggregating the effects of putatively functional low-frequency/rare variants. We then sought replication of the top findings in 1192 adults (European ancestry) with whole exome/genome sequencing data from 2 independent studies. Results- At 17q25, we confirmed the association of multiple common variants in TRIM65, FBF1, and ACOX1 ( P<6×10
Indexed as
BrainCohort StudiesExomeGenetic VariationHumansMagnetic Resonance ImagingMitochondrial ProteinsWhite MatterMitochondrial Proteinscerebral small vessel diseaseexomemagnetic resonance imagingmeta-analysiswhite matter
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