Keypoint: Men have a higher ASD heritability estimate than women, even after controlling for birth year and parental age.
The heritability of autism spectrum disorder (ASD) is higher among men than women, according to new research published in JAMA Psychiatry. Given these findings, study authors discuss the possible scenarios that may explain the observed sex differences in the genetic variance of ASD.
It has been widely established that ASD is more prevalent among boys and men than girls and women. However, previous genetic research has not fully elucidated estimates of ASD heritability by sex using a large, population-based database. To this aim, investigators conducted a population-based familial heritability analysis using Swedish national register data.
The investigators identified non-twin siblings and cousins born in Sweden between January 1, 1985, and December 31, 1998 and followed up all individuals until they reached 19 years of age to optimize detection of ASD diagnoses. International Classification of Diseases (ICD) codes were used to confirm ASD diagnoses from specialist care or inpatient treatment. The primary outcome of interest was an ASD heritability estimation a result of sex-specific additive genetics, shared environmental effects, and a common residual term.
The investigators included 1,047,649 individuals in 456,832 families for analysis, 48.62% of which were women (n=509,366). By 19 years of age, 12,226 individuals (1.17%) were diagnosed with ASD, including 8128 men (1.51%) and 4098 women (0.80%).
The investigators observed a higher cumulative rate of ASD diagnoses for men compared with women. Additionally, ASD diagnoses were higher among individuals born between 1995 and 1998 (n=5327; 2.36%) relative to those born between 1985 and 1989 (n=1891; 0.46%).
For all statistic models, the shared environmental contributions to ASD heritability were close to 0 and not statistically significant, suggesting that the sex differences in ASD prevalence are instead due to genetic variance. In heritability estimates, overall autism heritability was estimated at 82.6% (95% CI, 78.7%-86.4%) after controlling for birth year and parental age. However, sex-specific heritability was 87.0% for men (95% CI, 81.4%-92.6%) and 75.7% for women (95% CI, 68.4%-83.1%), resulting in an 11.3% (95% CI, 1.0%-21.6%) difference.
Although researchers are unable to definitively determine the underlying reasons for these sex differences, the study authors posit that the greater prevalence of ASD among men may be due to additive genetic sources or an increased vulnerability to the same genetic contributions.
The present findings indicate a modest, but statistically significant, difference in autism heritability between men and women. The investigators concluded, “The skewed sex ratio in ASD may, partly, be explained by differences in genetic variance between sexes.”
These results may be limited, as the investigators included only the first 3 siblings or cousins born from each family and the analyses rely on untestable assumptions about the independence of case ascertainment and the separation of genetic and environmental factors.
Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author disclosures.
Note: This article originally appeared on Psychiatry Advisor