Evidence map›Paper›PMID 27007234›Full record

ArticleJAMA psychiatry2016

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women.

Divya Mehta, Felix C Tropf, Jacob Gratten, Andrew Bakshi, Zhihong Zhu, Silviu-Alin Bacanu, Gibran Hemani, Patrik K E Magnusson, Nicola Barban, Tõnu Esko and 62 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JAMA psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

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

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Using genetics for social science.Nature human behaviour · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

72 authors.

Divya MehtaQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Felix C TropfDepartment of Sociology, Interuniversity Center for Social Science Theory and Methodology, University of Groningen, Groningen, the Netherlands3Department of Sociology, Nuffield College, University of Oxford, Oxford, England.
Jacob GrattenQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Andrew BakshiQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Zhihong ZhuQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Silviu-Alin BacanuVirginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond5Department of Psychiatry, Virginia Commonwealth University, Richmond.
Gibran HemaniMedical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, England.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Nicola BarbanDepartment of Sociology, Nuffield College, University of Oxford, Oxford, England.
Tõnu EskoEstonian Genome Center, University of Tartu, Tartu, Estonia.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia.
Harold SniederDepartment of Epidemiology, University of Groningen, The University Medical Center Groningen, Groningen, the Netherlands.
Bryan J MowryQueensland Brain Institute, The University of Queensland, Brisbane, Australia10Queensland Centre for Mental Health Research, Wacol, Australia.
Kenneth S KendlerVirginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond5Department of Psychiatry, Virginia Commonwealth University, Richmond11Department of Human and Molecular Genetics, Virginia Commonwealth University, Richm.
Jian YangQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Peter M VisscherQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
John J McGrathQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
Melinda C MillsDepartment of Sociology, Nuffield College, University of Oxford, Oxford, England.
Naomi R WrayQueensland Brain Institute, The University of Queensland, Brisbane, Australia.
S Hong LeeQueensland Brain Institute, The University of Queensland, Brisbane, Australia12School of Environmental and Rural Science, University of New England, Armidale, Australia.
Schizophrenia Working Group of the Psychiatric Genomics Consortium, LifeLines Cohort Study, and TwinsUK
Ole A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway14Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Elvira BramonUniversity College London, London, England.
Richard BruggemanUniversity Medical Center Groningen, Department of Psychiatry, University of Groningen, Groningen, the Netherlands.
Joseph D BuxbaumDepartment of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, New York18Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York19Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York.
Murray J CairnsSchizophrenia Research Institute, Sydney, Australia22Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, Australia23School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.
Rita M CantorDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles.
C Robert CloningerDepartment of Psychiatry, Washington University in St Louis, St Louis, Missouri.
David CohenDepartment of Child and Adolescent Psychiatry, Assistance Publique Hôpitaux de Paris, Pierre and Marie Curie University, and Institute for Intelligent Systems and Robotics, Paris, France.
Benedicto Crespo-FacorroCIBERSAM, University Hospital Marqués de Valdecilla, University of Cantabria-IDIVAL, Department of Psychiatry, Santander, Spain28 Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain.
Ariel DarvasiDepartment of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lynn E DeLisiSchizophrenia Research Institute, Sydney, Australia30VA Boston Health Care System, Brockton, Massachusetts.
Timothy DinanDepartment of Psychiatry, University College Cork, Cork, Ireland.
Srdjan DjurovicNORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway33Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Gary DonohoeCognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland35Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Elodie DrapeauDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
Valentina Escott-PriceMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, Wales.
Nelson B FreimerCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.
Lyudmila GeorgievaMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, Wales.
Lieuwe de HaanDepartment of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Frans A HenskensSchizophrenia Research Institute, Sydney, Australia39School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle, Australia40Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, Australia.
Inge JoaRegional Centre for Clinical Research in Psychosis, Department of Psychiatry, Stavanger University Hospital, Stavanger, Norway.
Antonio JuliàRheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
Andrey KhruninInstitute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
Bernard LererDepartment of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Svetlana LimborskaInstitute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.
Carmel M LoughlandSchizophrenia Research Institute, Sydney, Australia22Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, Australia.
Milan MacekDepartment of Biology and Medical Genetics, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Sara MarsalRheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
Robert W McCarleyVA Boston Health Care System, Brockton, Massachusetts47Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, Scotland49Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, Scotland.
Andrew McQuillinMolecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, England.
Bela MeleghDepartment of Medical Genetics, University of Pécs, Pécs, Hungary52Szentagothai Research Center, University of Pécs, Pécs, Hungary.
Patricia T MichieSchizophrenia Research Institute, Sydney, Australia53School of Psychology, University of Newcastle, Newcastle, Australia.
Derek W MorrisCognitive Genetics and Therapy Group, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland35Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Kieran C MurphyDepartment of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
Inez Myin-GermeysCenter for Contextual Psychiatry, Department of Neuroscience, KU Leuven, Leuven, Belgium.
Ann OlincyDepartment of Psychiatry, University of Colorado Denver, Aurora.
Jim Van OsInstitute of Psychiatry, King's College London, London, England58Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, the Netherlands.
Christos PantelisSchizophrenia Research Institute, Sydney, Australia59Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Australia.
Danielle PosthumaDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, the Netherlands61Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University Medical Center.
Digby QuestedDepartment of Psychiatry, University of Oxford, Oxford, England.
Ulrich SchallSchizophrenia Research Institute, Sydney, Australia22Priority Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, Australia.
Rodney J ScottSchizophrenia Research Institute, Sydney, Australia23School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia64Hunter New England Health Service, Newcastle, Australia.
Larry J SeidmanDepartment of Psychiatry, Harvard Medical School, Boston, Massachusetts65Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston.
Draga TonchevaDepartment of Medical Genetics, Medical University, Sofia, Bulgaria.
Paul A TooneySchizophrenia Research Institute, Sydney, Australia23School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia67Priority Research Centre for Translational Neuroscience and Mental Health, University of Newcastle, Newcastle.
John WaddingtonMolecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Daniel R WeinbergerLieber Institute for Brain Development, Baltimore, Maryland70Department of Psychiatry and Behavioral Sciences, The Johns Hopkins School of Medicine, Baltimore, Maryland71Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, Maryland72.
Mark WeiserSheba Medical Center, Tel Hashomer, Israel.
Jing Qin WuSchizophrenia Research Institute, Sydney, Australia23School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.

Funding

Using genetic overlap to dissect the genetic architecture of psychiatric diseasesR21MH100560 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI BACANU, SILVIU-ALIN · 2014 to 2015
$358k
Department of Health PDA/02/06/016European Research Council 615603Medical Research Council G0901310Medical Research Council MC_UU_12013/1Medical Research Council MR/K026992/1Medical Research Council MR/L010305/1Medical Research Council MR/L023784/2NIMH NIH HHS R21 MH100560Wellcome Trust
6 · The paper itself

Abstract

importanceA recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.

objectiveTo determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. DESIGN, SETTING, AND

participantsThis investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. MAIN OUTCOMES AND MEASURES: We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.

resultsWe observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.

Indexed as

Birth OrderGenome-Wide Association StudyMaternal AgeAdultAllelesCohort StudiesDenmarkFemaleGenetic Predisposition to DiseaseHumansPhenotypePregnancyRiskSchizophrenia

Identifiers

PMID27007234
PMCPMC5785705

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.