Four times as many males as females are afflicted with autism. Although there is much speculation about this sex bias, there have not been many well-powered studies designed to identify female genetic susceptibilities and differentiate them from male risk factors. Lauren Weiss and her colleagues at the University of California, San Francisco, set out to map the difference between male and female autism at the level of DNA. Understanding sexual dimorphism at this level may suggest ways to reduce autism risk for males and females.

Although genetic collections of males with autism are quite large, many fewer females are studied. Therefore, the researchers’ first task was to recruit as many females as possible to participate in their study. Once the researchers collected a sufficient number of samples from each sex, they began to examine several hypotheses.

Previous data show that females diagnosed with autism tend to be more severely affected than males. Perhaps there are different kinds of DNA variants in affected females compared with affected males. For example, females may be more susceptible to large deletions of genetic material or severe mutations in contrast with the milder polymorphic risk alleles seen in males. A second hypothesis is that sexually dimorphic factors such as the hormonal milieu or a second X chromosome instead of a Y may make some of the same genes confer different risk for autism in females and males. Weiss’s group is therefore searching for sex-specific or sex-biased risk factors on non-sex chromosomes.