Evidence map›Paper›PMID 27132484›Full record

ArticleSchizophrenia research2016

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study.

Steven P Millard, Jane Shofer, David Braff, Monica Calkins, Kristin Cadenhead, Robert Freedman, Michael F Green, Tiffany A Greenwood, Raquel Gur, Ruben Gur and 15 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Schizophrenia research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

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

25 authors.

Steven P MillardVISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; VISN-20 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
Jane ShoferVISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; VISN-20 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
David BraffVISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Monica CalkinsDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Kristin CadenheadDepartment of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Robert FreedmanDepartment of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, USA.
Michael F GreenDepartment of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA; VA Greater Los Angeles Health Care System, Los Angeles, CA, USA.
Tiffany A GreenwoodDepartment of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Raquel GurDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Ruben GurDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Laura C LazzeroniDepartment of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
Gregory A LightVISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Ann OlincyDepartment of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, USA.
Keith NuechterleinDepartment of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Larry SeidmanMassachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, MA, USA.
Larry SieverDepartment of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA; VISN-3 Mental Illness Research, Education, and Clinical Center, James J. Peters VA Medical Center, New York, NY, USA.
Jeremy SilvermanDepartment of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA; VISN-3 Mental Illness Research, Education, and Clinical Center, James J. Peters VA Medical Center, New York, NY, USA.
William S StoneMassachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry, Boston, MA, USA.
Joyce SprockVISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Catherine A SugarDepartment of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA; VA Greater Los Angeles Health Care System, Los Angeles, CA, USA; Department of Biostatistics, Fielding School of Public Health at University of California, Los Angeles, Los Angeles, CA, USA.
Neal R SwerdlowDepartment of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Ming TsuangDepartment of Psychiatry, University of California, San Diego, San Diego, CA, USA.
Bruce TuretskyDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Allen RadantVISN-20 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Debby W TsuangVISN-20 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Electronic address: dwt1@uw.edu.

Funding

The Genetics of Endophenotypes and SchizophreniaR01MH065571 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRAFF, DAVID L. · 2003 to 2013
$7.0M
SENSORY GATING &HABITUATION IN SCHIZOPHRENIAR01MH042228 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRAFF, DAVID L. · 1987 to 2015
$6.5M
The Genetics of Endophenotypes and SchizophreniaR01MH065578 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 2003 to 2013
$4.2M
The Genetics of Endophenotypes and SchizophreniaR01MH065554 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SIEVER, LARRY J · 2003 to 2013
$4.1M
Genetics of Endophenotypes and SchizophreniaR01MH065558 · NIMH · UNIVERSITY OF WASHINGTON · PI TSUANG, DEBBY WEN · 2003 to 2013
$3.7M
The Genetics of Endophenotypes and SchizophreniaR01MH065707 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GREEN, MICHAEL F. · 2003 to 2013
$3.6M
The Genetics of Endophenotypes and SchizophreniaR01MH065562 · NIMH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SEIDMAN, LARRY J · 2003 to 2007
$2.6M
The Genetics of Endophenotypes and SchizophreniaR01MH065588 · NIMH · UNIVERSITY OF COLORADO DENVER · PI OLINCY, ANN · 2003 to 2007
$2.2M
6/6 - The Genetics of Endophenotypes and SchizophreniaR01MH086135 · NIMH · STANFORD UNIVERSITY · PI LAZZERONI, LAURA C. · 2010 to 2013
$1.3M
Deep Sequencing in SchizophreniaI01BX002241 · VA · VA PUGET SOUND HEALTHCARE SYSTEM · PI TSUANG, DEBBY WEN · 2014 to 2017
–
BLRD VA I01 BX002241Intramural VA VA999999NIMH NIH HHS R01 MH042228NIMH NIH HHS R01 MH065554NIMH NIH HHS R01 MH065558NIMH NIH HHS R01 MH065562NIMH NIH HHS R01 MH065571NIMH NIH HHS R01 MH065578NIMH NIH HHS R01 MH065588NIMH NIH HHS R01 MH065707NIMH NIH HHS R01 MH086135
6 · The paper itself

Abstract

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially.

Indexed as

EndophenotypesSchizophrenic PsychologyAdolescentAdultAgedFamilyFemaleHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisNeuropsychological TestsROC CurveSchizophreniaYoung AdultAccuracyEndophenotypeLogistic regressionMultiple imputationRandom forestROC curveSchizophreniaSensitivitySpecificity

Identifiers

PMID27132484
PMCPMC4912929

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.