Evidence map›Paper›PMID 35312124›Full record

ArticleDepression and anxiety2022

Whole-exome DNA sequencing in childhood anxiety disorders identifies rare de novo damaging coding variants.

Emily Olfson, Eli R Lebowitz, Grace Hommel, Neha Pashankar, Wendy K Silverman, Thomas V Fernandez

Open access · greenAbstract read
In one paragraph

Article in Depression and anxiety, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Emily OlfsonChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0002-6438-0079
Eli R LebowitzChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0001-6240-4738
Grace HommelChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Neha PashankarChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Wendy K SilvermanChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-4415-4098
Thomas V FernandezChild Study Center, Yale University School of Medicine, New Haven, Connecticut, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8M
TRAINING PROGRAM IN CHILDHOOD NEUROPSYCHIATRIC DISORDERST32MH018268 · NIMH · YALE UNIVERSITY · PI Michael H Bloch, MICHAEL J CROWLEY · 1985 to 2026
$11.0M
Targeting Attention Orienting to Social Threat to Reduce Social Anxiety in YouthR01MH119299 · NIMH · FLORIDA INTERNATIONAL UNIVERSITY · PI PETTIT, JEREMY W, SILVERMAN, WENDY K. · 2019 to 2023
$5.7M
Research Training for Medical Students & Physician-Scientists in Child PsychiatryR25MH077823 · NIMH · YALE UNIVERSITY · PI ANDRES S MARTIN · 2006 to 2026
$4.0M
Neurogenetic Investigations of Obsessive-Compulsive DisorderR01MH114927 · NIMH · YALE UNIVERSITY · PI FERNANDEZ, THOMAS V · 2018 to 2022
$2.8M
Brain response associated with parent-based treatment for childhood anxiety disordersR61MH115113 · NIMH · YALE UNIVERSITY · PI GEE, DYLAN GRACE, LEBOWITZ, ELI · 2018 to 2019
$1.5M
Fibroblast Growth Factor 2's role in Fear and Approach Motivation in Anxious and Depressed Children and their MothersR21MH113946 · NIMH · YALE UNIVERSITY · PI LEBOWITZ, ELI, SILVERMAN, WENDY K. · 2017 to 2018
$461k
NCATS NIH HHS UL1 TR001863NHGRI NIH HHS UM1 HG006504NHGRI NIH HHS UM1HG006504NIMH NIH HHS R01 MH114927NIMH NIH HHS R01MH114927NIMH NIH HHS R01 MH119299NIMH NIH HHS R01MH119299NIMH NIH HHS R21 MH113946NIMH NIH HHS R21MH113946NIMH NIH HHS R25 MH077823NIMH NIH HHS R25MH077823NIMH NIH HHS R61 MH115113NIMH NIH HHS T32 MH018268NIMH NIH HHS T32MH018268
6 · The paper itself

Abstract

backgroundGenetic factors contribute to the development of anxiety disorders, yet few risk genes have been previously identified. One genomic approach that has achieved success in identifying risk genes in related childhood neuropsychiatric conditions is investigations of de novo variants, which has yet to be leveraged in childhood anxiety disorders.

methodsWe performed whole-exome DNA sequencing in 76 parent-child trios (68 trios after quality control) recruited from a childhood anxiety disorder clinic and compared rates of rare and ultra-rare de novo variants with 790 previously sequenced control trios (783 trios after quality control). We then explored overlap with risk genes for other neuropsychiatric conditions and enrichment in biologic pathways.

resultsRare and ultra-rare de novo likely gene disrupting and predicted damaging missense genetic variants are enriched in anxiety disorder probands compared with controls (rare variant rate ratio 1.97, 95% confidence interval [CI]: 1.11-3.34, p = .03; ultra-rare variant rate ratio 2.59, 95% CI: 1.35-4.70, p = .008). These de novo damaging variants occur in individuals with a variety of childhood anxiety disorders and impact genes that have been associated with other neuropsychiatric conditions. Exploratory network analyses reveal enrichment of deleterious variants in canonical biological pathways.

conclusionsThese findings provide a path for identifying risk genes and promising biologic pathways in childhood anxiety disorders by de novo genetic variant detection. Our results suggest the discovery potential of applying this approach in larger anxiety disorder cohorts to advance our understanding of the underlying biology of these common and debilitating conditions.

Indexed as

Biological ProductsExomeAnxiety DisordersGenetic Predisposition to DiseaseHumansSequence Analysis, DNABiological Productsanxiety disordersbiologic pathwayschildhoodde novoexome sequencinggenomicsrare variants

Identifiers

PMID35312124
PMCPMC9246845
OpenAlexW4220657433

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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.