Sex Ratios in Autism, an Analysis of 8,167 Participants in the International Autism Mapping Project

Background: Estimates of autism spectrum disorder in the US are currently 1 in 59 children, with male to female ratios approximating 4:1. Autism spectrum disorder (ASD) includes a diversity of causal factors such as birth prematurity, Fragile X, single gene mutations, CNS infection and injury at birth. The reasons for the male predominance aren’t clear. A more granular look at sex ratios may help.

Objectives: This study aimed to understand and characterize medical and genetic issues in children with a diagnosis of ASD, in an international sample of 8,167 children.

Methods: An archival dataset from the International Autism Mapping Project was examined. All parents who participated had a child with a confirmed diagnosis of autism born in the year 2000 or later and valid consent. This study nests within a larger study examining environmental factors in ASD. Within the environmental health questionnaire, parents were asked if their child had other genetic or medical diagnoses. Answers to that question were broken down into one of five categories, 1) single gene mutations, 2) multiple gene mutations, 3) known medical conditions or chromosomal disorders, 4) reported medical conditions or genetic conditions which lacked full specificity and 5) children who have multiple syndromes or conditions. Tables 1, 2, 3 include the number, gender, general inheritance pattern, and association to emotional-behavioral health. Sex ratios were examined, with X-linked conditions removed and treated separately.

Results: Of 8,167 records, 105 parents reported single gene mutations. The male to female ratio for this group is 2.62:1. Here, methylenetetrahydrofolate reductase (MTHFR) gene mutations were the most common genetic issue with 14 males and 8 females. Another frequent diagnosis was 22q11.2 deletion syndrome, with 15 males and 5 females. In the multiple gene mutation group, there were 52 children, with an overall male to female ratio of 3:1. In our 3^rd grouping, of known medical conditions or chromosomal disorders, there are 177 children, with a general male to female ratio of 2.76:1. Here an unexpected finding involved Down syndrome, with 20 males and 4 females. Premature birth, defined as <32 weeks gestation, was reported for 27 children, with male to female ratio of 2.37:1. In our 4^th grouping of 29 children, parents had reported issues not specific enough for full categorization; the male to female ratio for the group 3.83:1. In the 5^th group, those with multiple conditions or syndromes, were 29 children, and here the male to female ratio is 4.6:1.

All tables will be presented.

Conclusions: The commonly reported sex ratio for children with autism is 4:1, with males predominating. In a more granular examination, this ratio varied considerably. Further, we found that in conditions thought to occur more or less equally between the sexes, the ratio was unexpectedly strongly biased towards males. Ratios were 3:1 in 22q11.2 deletion syndrome, 5:1 in Down syndrome, and 2.37:1 in prematurity. To what extent these striking asymmetries reflect bias in diagnosing ASD or sex-biasing genetic factors is unknown.