Advanced Paternal Age and Early Onset of Schizophrenia in Sporadic Cases: Not Confounded by Parental Polygenic Risk for Schizophrenia.

Adult Age of Onset Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Multifactorial Inheritance Paternal Age Risk Factors Schizophrenia / epidemiology
De novo mutation GWAS Paternal age Polygenic risk score Schizophrenia Selection into late fatherhood

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
01 07 2019
Historique:
received: 07 07 2018
revised: 24 01 2019
accepted: 24 01 2019
pubmed: 31 3 2019
medline: 11 6 2020
entrez: 31 3 2019
Statut: ppublish

Résumé

Whether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium. Among 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents' genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients' early onset of schizophrenia (≤18 years old) on paternal age was conducted. Advanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients' early onset of schizophrenia remained (odds ratio = 1.29, p = .04). The association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

Sections du résumé

BACKGROUND
Whether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium.
METHODS
Among 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents' genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients' early onset of schizophrenia (≤18 years old) on paternal age was conducted.
RESULTS
Advanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients' early onset of schizophrenia remained (odds ratio = 1.29, p = .04).
CONCLUSIONS
The association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

Identifiants

DOI: 10.1016/j.biopsych.2019.01.023 PMID: 30926130
pubmed: 30926130
pii: S0006-3223(19)30069-1
doi: 10.1016/j.biopsych.2019.01.023
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

56-64

Subventions

Organisme : NHGRI NIH HHS
ID : U54 HG003067
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085521
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085560
Pays : United States

Informations de copyright

Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Auteurs

Shi-Heng Wang (SH)

Departments of Public Health and Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan.

Po-Chang Hsiao (PC)

Institute of Epidemiology and Preventive Medicine, College of Public Health, Taipei, Taiwan.

Ling-Ling Yeh (LL)

Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan.

Chih-Min Liu (CM)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Chen-Chung Liu (CC)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Tzung-Jeng Hwang (TJ)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Ming H Hsieh (MH)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Yi-Ling Chien (YL)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Yi-Ting Lin (YT)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Yen-Tsung Huang (YT)

Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

Chia-Yen Chen (CY)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Sharon D Chandler (SD)

Center for Behavioral Genomics, Department of Psychiatry and Institute for Genomic Medicine, University of California San Diego, La Jolla, California.

Stephen V Faraone (SV)

Departments of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, Medical Genetics Research Center, State University of New York Upstate Medical University, Syracuse, New York.

Benjamin Neale (B)

Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Stephen J Glatt (SJ)

Departments of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, Medical Genetics Research Center, State University of New York Upstate Medical University, Syracuse, New York.

Ming T Tsuang (MT)

Center for Behavioral Genomics, Department of Psychiatry and Institute for Genomic Medicine, University of California San Diego, La Jolla, California.

Hai-Gwo Hwu (HG)

Department of Psychiatry, College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Institute of Brain and Mind Sciences, College of Medicine, Taipei, Taiwan.

Wei J Chen (WJ)

Institute of Epidemiology and Preventive Medicine, College of Public Health, Taipei, Taiwan; Department of Public Health, College of Public Health, Taipei, Taiwan; Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: wjchen@ntu.edu.tw.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs âges › Âge de début › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Âge paternel › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Advanced Paternal Age and Early Onset of...
questionsmedicales.fr › Troubles mentaux › Schizophrénie et troubles avec traits psychotiques › Schizophrénie › Advanced Paternal Age and Early Onset of...