Risk for Autism is Increased with Paternal Age in an Iranian Population Sample

Background:

The etiology of idiopathic autism is still unclear and, despite its strong heritability, few susceptibility genes have been identified. Evidence from several epidemiological studies has implicated paternal age as a risk factor for autism. Recently implemented population screening for autism in Iran allowed us to conduct a large-scale epidemiological study.

Objectives:

To determine whether increasing paternal age is associated with increased risk for autism in an Iranian population sample.

Methods:

The sample consists of 747,403 controls and 229 autism spectrum disorder (ASD) cases obtained from the Special Education Organization of Iran. Cases and controls were 5-12 years of age. ASD diagnoses were made according to DSM-IV criteria and standard diagnostic instruments. Analyses used logistic regression, adjusting for maternal age, paternal and maternal education, birth order, consanguinity, and sex.

Results:

We found a significantly increased risk for ASD with increasing paternal age. Compared with a paternal age of 30 and under, the odds ratio (OR) for paternal age 36-40 was 2.20 (95% CI: 1.09, 4.45), while the OR for paternal age greater than 40 was 2.67; 95% CI: 1.07, 6.64). Paternal age category 31-35 also showed a similar but non-significant trend for increased risk (OR: 1.55; 95% CI: 0.90, 2.67). There was no increased risk for autism with increasing maternal age.

Conclusions:

In this Iranian population sample, paternal age greater than 35 was associated with an approximately 2-3 fold increase in the risk for autism. This effect was independent of maternal age, paternal and maternal education, birth order, consanguinity, and sex. There are several possible explanations for these results, such as that mutations are more likely to occur or accumulate in the germ line DNA of older men, and/or genes transmitted by older fathers may be improperly imprinted, leading to abnormal functioning of these genes.