Evidence map›Paper›PMID 38697120›Full record

ArticleCell genomics2024

Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.

Patrick B Chen, Rachel Chen, Nathan LaPierre, Zeyuan Chen, Joel Mefford, Emilie Marcus, Matthew G Heffel, Daniela C Soto, Jason Ernst, Chongyuan Luo and 1 more

Abstract read
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Patrick B ChenDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Rachel ChenDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nathan LaPierreDepartment of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Zeyuan ChenDepartment of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
Joel MeffordDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Emilie MarcusDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
Matthew G HeffelDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Daniela C SotoDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jason ErnstDepartment of Computer Science, Samueli School of Engineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
Chongyuan LuoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jonathan FlintDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: jflint@mednet.ucla.edu.

Funding

Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brainsU01MH130995 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Chongyuan Luo, Mercedes Paredes · 2022 to 2026
$4.4M
SINGLE-CELL MULTI-OMIC APPROACHES TO MECHANISTICALLY CHARACTERIZE PSYCHIATRIC DISORDER RISK LOCI IN THE HUMAN BRAINR01MH125252 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUO, CHONGYUAN · 2021 to 2025
$3.7M
Developing a Pathway from Genetic Locus to Gene for Complex Traits in RodentsR01MH115979 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FLINT, JONATHAN · 2018 to 2022
$3.5M
Deciphering the Relationship between Substance Use and Psychiatric Disorders from Whole Genome Sequencing DataDP1DA044371 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ERNST, JASON · 2017 to 2021
$2.3M
NIDA NIH HHS DP1 DA044371NIMH NIH HHS R01 MH115979NIMH NIH HHS R01 MH125252NIMH NIH HHS U01 MH130995NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.

Indexed as

FearQuantitative Trait LociAnimalsBehavior, AnimalChromosome MappingFemaleGenetic Complementation TestMaleMiceMice, Inbred C57BLfear conditioninginbred mouse strainsQTL mappingquantitative complementationsingle-nucleus ATAC-seqsingle-nucleus RNA-seq

Identifiers

PMID38697120
PMCPMC11099346

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.