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


METHODS
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.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University,Taipei,Taiwan.
S H
SH
Wang
Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University,Taipei,Taiwan.
C M
CM
Liu
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University,Taipei,Taiwan.
H G
HG
Hwu
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University,Taipei,Taiwan.
C K
CK
Hsiao
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University,Taipei,Taiwan.
W J
WJ
Chen
D000328:Adult; D017677:Age Distribution; D020022:Genetic Predisposition to Disease; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D012044:Regression Analysis; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D035781:Siblings / Q000523:psychology*; D013624:Taiwan; D055815:Young Adult
Age at onset; co-affected sib-pairs; familial predisposition; paternal age; schizophrenia; spontaneous mutation