| Advancing paternal age and the risk of schizophrenia. | |
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MedLine Citation:
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PMID: 11296097 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: A major source of new mutations in humans is the male germ line, with mutation rates monotonically increasing as father's age at conception advances, possibly because of accumulating replication errors in spermatogonial cell lines. METHOD: We investigated whether the risk of schizophrenia was associated with advancing paternal age in a population-based birth cohort of 87 907 individuals born in Jerusalem from 1964 to 1976 by linking their records to the Israel Psychiatric Registry. RESULTS: Of 1337 offspring admitted to psychiatric units before 1998, 658 were diagnosed as having schizophrenia and related nonaffective psychoses. After controlling for maternal age and other confounding factors (sex, ethnicity, education [to reflect socioeconomic status], and duration of marriage) in proportional hazards regression, we found that paternal age was a strong and significant predictor of the schizophrenia diagnoses, but not of other psychiatric disorders. Compared with offspring of fathers younger than 25 years, the relative risk of schizophrenia increased monotonically in each 5-year age group, reaching 2.02 (95% confidence interval, 1.17-3.51) and 2.96 (95% confidence interval, 1.60-5.47) in offspring of men aged 45 to 49 and 50 years or more, respectively. Categories of mother's age showed no significant effects, after adjusting for paternal age. CONCLUSIONS: These findings support the hypothesis that schizophrenia may be associated, in part, with de novo mutations arising in paternal germ cells. If confirmed, they would entail a need for novel approaches to the identification of genes involved in schizophrenia. |
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Authors:
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D Malaspina; S Harlap; S Fennig; D Heiman; D Nahon; D Feldman; E S Susser |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of general psychiatry Volume: 58 ISSN: 0003-990X ISO Abbreviation: Arch. Gen. Psychiatry Publication Date: 2001 Apr |
Date Detail:
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Created Date: 2001-04-11 Completed Date: 2001-04-26 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372435 Medline TA: Arch Gen Psychiatry Country: United States |
Other Details:
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Languages: eng Pagination: 361-7 Citation Subset: AIM; IM |
Affiliation:
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New York State Psychiatric Institute, 1051 Riverside Dr, New York, NY 10032, USA. dm9@Columbia.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Age Factors Cohort Studies Female Humans Incidence Israel / epidemiology Male Marriage Maternal Age Middle Aged Mutation Paternal Age* Proportional Hazards Models Psychotic Disorders / epidemiology, genetics Schizophrenia / epidemiology*, genetics Sex Factors |
| Grant Support | |
ID/Acronym/Agency:
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M01 RR00096/RR/NCRR NIH HHS; MH01699 K24/MH/NIMH NIH HHS; R01 MH59114/MH/NIMH NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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