Autism is a highly genetic neurodevelopmental condition (heritability > 80% (Bai et al. 2019)) affecting an estimated 1 in 44 children in the U.S. every year (Maenner et al. 2021). Research into the biology underlying autism has primarily focused on the core symptoms defined by the DSM (Association 2013): social communication challenges and restricted or repetitive behaviors. However, less is known about the genetic factors influencing other mental health comorbidities in autism, the most alarming being suicidal ideation, self-harm, and death by suicide.

Previous studies of autism found profoundly increased rates of suicide and depression (Hirvikoski et al. 2016), (Kato et al. 2013), (Hedley et al. 2018), (Hudson, Hall, and Harkness 2019). The rate of death by suicide has been estimated to be 7.5 times higher in autistic people than those without an autism diagnosis (Hirvikoski et al. 2016). While rates of suicide death in autistic individuals have varied across samples (0.17-0.4% (Kirby et al., 2019, Kõlves et al., 2021)) they are consistently higher than rates observed in non-autistic individuals. The increased suicide rate in autism may be partially attributable to a broad increase in depressive symptoms, as autistic people have been shown to have a 4-fold increase in lifetime rates of depression (Hudson, Hall, and Harkness 2019). Known protective factors against suicide death, like education, age, and marriage, are not protective in autistic samples (Kõlves et al. 2021). Furthermore, this mental illness burden may be exacerbated by exceptional cognitive ability: in other work, we found that children with a exceptional IQ (≥120) and autism have greater feelings of inadequacy and internalizing problems compared to autistic individuals with average IQ (Michaelson et al. 2021). These findings contrast with findings in non-autistic cohorts, where large population studies have found high IQ is a protective factor against suicide death (Batty et al., 2010, Wallin et al., 2018), suggesting that the relationship between intelligence and suicide-related traits may vary across diagnostic boundaries.

There is evidence that suicide risk is partly genetic in nature, with heritability estimates ranging from 17-55% (Vaquero-Lorenzo and Vasquez 2020). Some evidence for potential mechanistic overlap between the biology of suicide and of autism comes from a study that identified mutations in a well-known autism risk gene, NRXN1, as increasing risk for suicide (William et al. 2021). In a general population study (which included autistic individuals) increased polygenic risk for autism was found to be positively associated with suicidal thoughts. Furthermore, autistic children with suicidal thoughts inherit more genetic risk factors for self-harm ideation than expected (Warrier and Baron-Cohen 2021), lending further evidence to potential shared biological mechanisms between suicide and autism. Although connected to autism through these modes of genetic risk, it is unknown what other factors might also contribute to the excess burden of suicidality seen in autism and how these compare to age matched controls.

This previous work points to several key questions, which we aim to address in this study: do autistic children show increased signs of suicidal ideation or self-harm compared to peers? Are suicidal thoughts related to elevated cognitive ability in autistic children? What modes of genetic risk are associated with depressive and suicidal traits in autistic children? In seeking to answer these questions, we assembled evidence from multiple samples: a clinical sample of high academic achievers with neurodevelopmental conditions (Michaelson et al. 2021), the Adolescent Brain Cognitive Development study (ABCD, (Lisdahl et al. 2018)), a general population sample, and SPARK - a nationwide study of autism (Feliciano et al. 2018). Answering these questions will offer new insight into autism-relevant risk factors and the interplay and trade-offs between intelligence, neurodiversity, and mental illness, while also drawing attention to clinically meaningful subgroups most at risk for suicide. To our knowledge, this is the first study to examine the relationship between autism, exceptional cognitive ability, suicidal thoughts, and genetics across multiple large samples of children.

Many autistic self-advocates prefer identity-first language (i.e., autistic individuals), and some autistic individuals and their families prefer person-first language (i.e., individuals with autism). We recognize the validity of the arguments behind both of these preferences, and have chosen to use identity-first language for this paper.