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Association of older paternal age with earlier onset among co-affected schizophrenia sib-pairs

Published online by Cambridge University Press:  09 March 2015

S. H. Wang ,
C. M. Liu ,
H. G. Hwu ,
C. K. Hsiao  and
W. J. Chen
S. H. Wang
Affiliation:
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Genetic Epidemiology Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
C. M. Liu
Affiliation:
Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
H. G. Hwu
Affiliation:
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
C. K. Hsiao
Affiliation:
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Genetic Epidemiology Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan
W. J. Chen*
Affiliation:
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Genetic Epidemiology Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Psychiatry, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
*
*Address for correspondence: W. J. Chen, M.D., Sc.D., Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 17 Xu-Zhou Road, Taipei 100, Taiwan. (Email: wjchen@ntu.edu.tw)
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Abstract

Background

Advanced paternal age is associated with increased risk of schizophrenia. This study aimed to explore whether older paternal age is associated with earlier onset among co-affected schizophrenia sib-pairs with the same familial predisposition.

Method

A total of 1297 patients with schizophrenia from 630 families, which were ascertained to have at least two siblings affected, throughout Taiwan were interviewed using the Diagnostic Interview for Genetic Studies. Both inter-family comparisons, a hierarchical regression model allowing for familial dependence and adjusting for confounders, and within-family comparisons, examining the consistency between onset order and birth order, were performed.

Results

An inverted U shape was observed between paternal age and onset of schizophrenia. Affected offspring with paternal age of 20–24 years had the oldest onset. As paternal age increased over 25 years, older paternal age exhibited a linear decrease in the onset of schizophrenia. On average, the onset was lowered by 1.5 years for paternal age of 25–29 years and by 5.5 years for paternal age ⩾50 years (p = 0.04; trend test). The proportion of younger siblings with earlier onset (58%) was larger than that of older siblings with earlier onset (42%) (p = 0.0002).

Conclusions

These findings indicate that paternal age older than 25 years and younger than 20 years were both associated with earlier onset among familial schizophrenia cases. The associations of advanced paternal age with both increased susceptibility to schizophrenia and earlier onset of schizophrenia are consistent with the rate of increases in spontaneous mutations in sperm as men age.

Keywords

Age at onsetco-affected sib-pairsfamilial predispositionpaternal ageschizophreniaspontaneous mutation
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 10 , July 2015 , pp. 2205 - 2213
Copyright
Copyright © Cambridge University Press 2015 

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