Evidence map›Paper›PMID 32912094›Full record

ArticleStroke2020

Exome Array Analysis of Early-Onset Ischemic Stroke.

Thomas Jaworek, Kathleen A Ryan, Brady J Gaynor, Patrick F McArdle, Oscar C Stine, Timothy D OConnor, Haley Lopez, Hugo J Aparicio, Yan Gao, Xiaochen Lin and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Stroke, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
0.4field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. 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

20 authors at 6 institutions in 1 country.

Thomas JaworekUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Kathleen A RyanUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Brady J GaynorUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Patrick F McArdleUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Oscar C StineUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Timothy D OConnorUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Haley LopezUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Hugo J AparicioBoston University School of Medicine, MA (H.J.A., Q.Y., S.S.).
Yan GaoUniversity of Mississippi Medical Center, Jackson (Y.G., J.W.).
Xiaochen LinBrown University, Providence, Rhode Island (X.L., S.L.).
Megan L GrovesThe University of Texas Health Science Center at Houston (M.L.G.).
Matthew L FlahertyThe University of Cincinnati College of Medicine, OH (M.L.F.).
Simin LiuBrown University, Providence, Rhode Island (X.L., S.L.).
Qiong YangBoston University School of Medicine, MA (H.J.A., Q.Y., S.S.).
James WilsonUniversity of Mississippi Medical Center, Jackson (Y.G., J.W.).
Sudha SeshadriBoston University School of Medicine, MA (H.J.A., Q.Y., S.S.).
Steven J KittnerUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Braxton D MitchellUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
Huichun XuUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
John W ColeUniversity of Maryland School of Medicine, Baltimore, MD (T.J., K.A.R., B.J.G., P.F.M., O.C.S., T.D.O., H.L., S.J.K., B.D.M., H.X., J.W.C.).
University of Maryland, Baltimore · USBoston University · USBrown University · USUniversity of Mississippi Medical Center · USThe University of Texas Health Science Center · USUniversity of Cincinnati Medical Center · US

Funding

FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
RESEARCH TRAINING IN THE EPIDEMIOLOGY OF AGINGT32AG000262 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI ANN L GRUBER-BALDINI, DENISE L ORWIG · 1998 to 2026
$8.2M
Genetics of ischemic stroke in the SiGN ConsortiumR01NS100178 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2017 to 2021
$3.0M
Genetics of Early-Onset Ischemic Stroke ConsortiumR01NS105150 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2018 to 2022
$3.0M
CNV And Stroke (CaNVAS)R01NS114045 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI COLE, JOHN W. · 2020 to 2024
$2.6M
BLRD VA I01 BX004672NHLBI NIH HHS 75N92019D00031NIA NIH HHS T32 AG000262NIDDK NIH HHS P30 DK072488NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS100178NINDS NIH HHS R01 NS105150NINDS NIH HHS R01 NS114045
6 · The paper itself

Abstract

background and purposeThe genetic contribution to ischemic stroke may include rare- or low-frequency variants of high-penetrance and large-effect sizes. Analyses focusing on early-onset disease, an extreme-phenotype, and on the exome, the protein-coding portion of genes, may increase the likelihood of identifying such rare functional variants. To evaluate this hypothesis, we implemented a 2-stage discovery and replication design, and then addressed whether the identified variants also associated with older-onset disease.

methodsDiscovery was performed in UMD-GEOS Study (University of Maryland-Genetics of Early-Onset Stroke), a biracial population-based study of first-ever ischemic stroke cases 15 to 49 years of age (n=723) and nonstroke controls (n=726). All participants had prior GWAS (Genome Wide Association Study) and underwent Illumina exome-chip genotyping. Logistic-regression was performed to test single-variant associations with all-ischemic stroke and TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtypes in Whites and Blacks. Population level results were combined using meta-analysis. Gene-based aggregation testing and meta-analysis were performed using seqMeta. Covariates included age and gender, and principal-components for population structure. Pathway analyses were performed across all nominally associated genes for each stroke outcome. Replication was attempted through lookups in a previously reported meta-analysis of early-onset stroke and a large-scale stroke genetics study consisting of primarily older-onset cases.

resultsGene burden tests identified a significant association with

conclusionsExome-based analysis in the setting of early-onset stroke is a promising strategy for identifying novel genetic risk variants, loci, and pathways.

Indexed as

AdolescentAdultAge of OnsetBlack or African AmericanExomeFemaleGene Regulatory NetworksGenome-Wide Association StudyHumansIschemic StrokeMaleMiddle AgedWhite PeopleYoung Adultearly-onsetexomeexonsglucosepenetrancesingle nucleotide polymorphismstroke

Identifiers

PMID32912094
PMCPMC7606344
OpenAlexW3086114716

What OpenQuestion holds

Textmetadata
LicenceTDM
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.