Evidence map›Paper›PMID 25824302›Full record

ArticleMolecular psychiatry2016

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

H Qin, J F Samuels, Y Wang, Y Zhu, M A Grados, M A Riddle, B D Greenberg, J A Knowles, A J Fyer, J T McCracken and 20 more

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

Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–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

26 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. The role of Pcdh10 in neurological disease and cancer.Journal of cancer research and clinical oncology · 2023
    Review
  10. Article
  11. Article
  12. Genetics of obsessive-compulsive disorder.Psychological medicine · 2021
    Review
  13. Article
  14. Pharmacotherapeutic Strategies and New Targets in OCD.Current topics in behavioral neurosciences · 2021
    Review
  15. Review
  16. Article
  17. Pharmacogenetics of Obsessive-Compulsive Disorder: An Evidence-Update.Current topics in behavioral neurosciences · 2021
    Review
  18. Article
  19. Review
  20. 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

30 authors.

H QinUnit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
J F SamuelsDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Y WangDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Y ZhuDepartment of Epidemiology, Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA.
M A GradosDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
M A RiddleDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
B D GreenbergDepartment of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
J A KnowlesDepartment of Psychiatry, Keck Medical School, University of Southern California, Los Angeles, CA, USA.
A J FyerCollege of Physicians and Surgeons, Columbia University, New York, NY, USA.
J T McCrackenDepartment of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, USA.
D L MurphyLaboratory of Clinical Science, NIMH, NIH, Bethesda, MD, USA.
S A RasmussenDepartment of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
B A CullenDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
J PiacentiniDepartment of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, USA.
D GellerDepartment of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
S E StewartDepartment of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
D PaulsDepartment of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Brown University, Providence, RI, USA.
O J BienvenuDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
F S GoesDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
B MaherDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
A E PulverDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
D ValleDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
C LangeDepartment of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
M MattheisenDepartment of Biostatistics, Harvard School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8442-493X
N C McLaughlinDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
K-Y LiangDepartment of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
E L NurmiDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Jane and Terry Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA, USA.
K D AsklandDepartment of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert School of Medicine of Brown University, Providence, RI, USA.
G NestadtDepartment of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Y Y ShugartUnit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

Funding

OCD Collaborative Genetics Association StudyR01MH071507 · NIMH · JOHNS HOPKINS UNIVERSITY · PI NESTADT, GERALD · 2007 to 2010
$6.5M
Obsessive-compulsive disorder (OCD) Collaborative Genetics Association StudyR01MH079489 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI GELLER, DANIEL A · 2007 to 2010
$3.4M
Developing new statisical methods to detect variants involved in complex diseaseZIAMH002929 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI YAO, YIN · 2011 to 2016
$2.6M
Developing Stats Methods to Detect Rare Genetics Variants in Human PedigreesZIAMH002930 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI YAO, YIN · 2011 to 2016
$1.6M
OCD Collaborative Genetics Association StudyR01MH079488 · NIMH · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FYER, ABBY J · 2007 to 2010
$906k
Statistical Genomics and Data Analysis CoreZIAMH002965 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI YAO, YIN · 2017 to 2017
$856k
Obsessive-compulsive disorder (OCD) Collaborative Genetics Association StudyR01MH079494 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KNOWLES, JAMES A · 2007 to 2011
$840k
OCD Collaborative Genetics Association StudyR01MH079487 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCCRACKEN, JAMES T. · 2007 to 2010
$797k
Intramural NIH HHS ZIA MH002930NIMH NIH HHS MH002930-04NIMH NIH HHS MH071507NIMH NIH HHS MH079487NIMH NIH HHS MH079488NIMH NIH HHS MH079489NIMH NIH HHS MH079494NIMH NIH HHS R01 MH071507NIMH NIH HHS R01 MH079487NIMH NIH HHS R01 MH079488NIMH NIH HHS R01 MH079489NIMH NIH HHS R01 MH079494
6 · The paper itself

Abstract

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.

Indexed as

AdolescentAdultAgedChildFemaleGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansLinkage DisequilibriumMaleMembrane ProteinsMiddle AgedObsessive-Compulsive DisorderPolymorphism, Single NucleotideSelective Serotonin Reuptake InhibitorsMembrane ProteinsSelective Serotonin Reuptake Inhibitors

Identifiers

PMID25824302
PMCPMC5027902

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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.