Evidence map›Paper›PMID 37038335›Full record

SynthesisNeuro-oncology2023

Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.

Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala and 4 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Neuro-oncology, 2023. 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
0.9field-weighted citation impact, top 24% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

14 authors at 3 institutions in 1 country.

Austin L BrownDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.ORCID 0000-0001-5802-5073
Pagna SokDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Kimberly P RaghubarDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Philip J LupoDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Melissa A RichardDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Alanna C MorrisonDepartment of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
Jun J YangDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-4233-3220
Clinton F StewartDepartment of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
Mehmet Fatih OkcuDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Murali M ChintagumpalaDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Amar GajjarDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Lisa S KahalleyDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.
Heather ConklinPsychology Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
Michael E ScheurerDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas.ORCID 0000-0002-8379-6088
Baylor College of Medicine · USSt. Jude Children's Research Hospital · USThe University of Texas Health Science Center at Houston · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9M
Cognitive Change after Proton RT vs. Photon or Surgery for Pediatric Brain TumorR01CA187202 · NCI · BAYLOR COLLEGE OF MEDICINE · PI KAHALLEY, LISA SCHUM · 2014 to 2019
$2.9M
Integrative Molecular Epidemiology of Neurocognitive Outcomes in Acute Lymphoblastic LeukemiaK07CA218362 · NCI · BAYLOR COLLEGE OF MEDICINE · PI BROWN, AUSTIN L · 2018 to 2022
$758k
NCI NIH HHS K07 CA218362NCI NIH HHS P30 CA021765NCI NIH HHS P30 CA21765NCI NIH HHS R01 CA187202
6 · The paper itself

Abstract

backgroundSurvivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

methodsIntelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

resultsParticipants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2-10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10-5; rs31771, P = 7.8 × 10-4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10-9), WM (rs17774009, meta-P = 4.2 × 10-9), and PS (rs77467524, meta-P = 1.5 × 10-8; rs17630683, meta-P = 2.0 × 10-8; rs73249323, meta-P = 3.1 × 10-8).

conclusionsInherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.

Indexed as

Brain NeoplasmsCentral Nervous System NeoplasmsCognitive DysfunctionCraniospinal IrradiationChildFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIntelligenceMalecognitive impairmentcraniospinal irradiationgeneticsintelligencepediatric brain tumor

Identifiers

PMID37038335
PMCPMC10479777
OpenAlexW4364352692

What OpenQuestion holds

Textmetadata
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.