The prevalence of symptoms and co-morbidities with ICD-9 codes corresponding to those diseases previously shown to be co-morbid with ASD are shown in , and Table S2
. Despite the nature of the tools in this study, the estimates obtained are consistent with those from prior studies. Within the group of individuals with ASD, Epilepsy (ICD-9 Diagnosis Code 345.*, see Table S1
) was found to have prevalence of 19.4%, schizophrenia 2.4% (83 ICD-9 codes listed in Table S1
), bowel disorders 11.7% (112 ICD-9 Codes excluding those for inflammatory bowel disease), inflammatory bowel disease 0.8% (ICD 9 555.* and 556.*), type 1 diabetes mellitus (subset of ICD9 250.* as in Table S1
) 0.8%, autoimmune disorders (which for the purpose of this study, specifically excludes IBD and type 1 diabetes mellitus—See Table S1
) 0.7%, and CNS/head anomalies (80 ICD-9 codes) 12.4%. Sleep disorders (ICD9 307.4*) at 1.1% were much lower than the prior estimates of 50% obtained in formal assessment of children with ASD 
. The prevalence of genetic disorders of Fragile X Syndrome, Tuberous Sclerosis and Down Syndrome in individuals with ASD prevalence of 0.5%, 0.8%, 0.9% is consistent with prior studies finding that single gene disorders are responsible for only small fractions of ASD even if collectively they might exceed 20% 
. Many other genetic syndromes could not be assessed in this study because there was no corresponding ICD-9 code. For other EMR analysis projects we have successfully used natural language processing (NLP) techniques across the clinical notes for these “uncoded” syndromes. Such an approach, which takes considerable time and effort to ensure the accuracy of each phenotype 
, was beyond the scope of this investigation. Also is shown the prevalence of ASD in these same co-morbidities where the aforementioned genetic disorders had ASD prevalences of 21%, 10.8%, and 3.1% respectively. Several other co-morbidities had ASD prevalence of greater than 5% including CNS anomalies (6.3%), epilepsy (5.3%), and schizophrenia (6.1%)
Characteristics of the ASD population studied.
Prevalence of co-morbidities of autism and prevalence of autism in these comorbidities.
When prevalence of these co-morbidities in ASD were compared to their prevalence in the general population captured by this study (i.e. individuals with at least one inpatient or outpatient visit to one of the four hospitals and therefore enriched for diseases in the population less than 35 years of age—), all the above disorders were found to be at significantly higher counts (Pearson's chi-square, p<0.0001, 95% confidence intervals shown in ) except for autoimmune disorders (in ASD at 0.67% vs 0.68%, p<0.97). Even though the category of autoimmune disorders was not significantly greater than the general population, the autoimmune disorders excluded from this category: type 1 diabetes mellitus and IBD were significantly enriched. Also, bowel disorders were found to be significantly increased, a point of some divergence in prior studies 
. Although the prevalence of sleep disorders in ASD was found to be lower than in prior studies, it nonetheless was approximately ten-fold higher than the general (hospital) population, as was schizophrenia. Muscular dystrophy was almost ten times more prevalent in the ASD population than in the general population, providing quantification absent in prior associations.
Comorbidities in autism vs same morbidities in the general hospital population.
Proportions of morbidity in the subpopulation with ASD and that of the hospital population.
A question increasingly asked is how does the comorbidity landscape of ASD change as children become young adults 
? Consequently we stratified the study population into two age ranges: 0–17 years and 18–34 years. Three co-morbidities did not change significantly with age (using p<0.01 as threshold due to multiple hypothesis testing): bowel disorders (11.63% to 12.97% p
<0.13), sleep disorders (1.25% to 0.41% p<0.05), and epilepsy (19.17% to 21.45% p<0.05). In contrast DM1 (0.67 to 2.08% p<4.5×10−10
), IBD (0.68% to1.99% p<9.7×10−9
) and schizophrenia (1.43% to 8.76%, p<3.1×10−79
) were significantly different, as in . Excluding DM1 and IBD, the other autoimmune disorders did not increase with age.
Comorbidities of ASD in younger (0–17 years) vs older (18–34 years).
Although unsurprising, the male to female ratio in this large sample was very close to 4
1 (see ).
As an additional comparison, we conducted the parallel co-morbidity study for fractures of the lower limb (FxLL) as performed for ASD (see Table S3
). All co-morbidities in ASD were significantly higher than those for FxLL with two exceptions: autoimmune disorders (excluding IBD and DM1 but including rheumatological disorders such as rheumatoid arthritis and systemic lupus erythematosus) and DM1. There are several decades of documentation of the higher prevalence of FxLL in both DM1 
and the rheumatological diseases (e.g Kim et al.