Data from: Psychiatric disorders in C9orf72 kindreds: study of 1,414 family members
Devenney, Emma M. et al. (2019), Data from: Psychiatric disorders in C9orf72 kindreds: study of 1,414 family members, Dryad, Dataset, https://doi.org/10.5061/dryad.1nd7372
Objective: This study aimed to determine in a systematic manner if the C9orf72 phenotype might extend beyond frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) to include psychiatric disease. Methods: A validated semi-structured family history interview was conducted in a large cohort of patients with FTD and ALS (n=89), with and without the C9orf72 expansion (n=29 and n=60 respectively) encompassing 1,414 first and second-degree relatives. Statistical analyses employed both the hazard ratio (HR) and relative risk ratio (RR) to determine the risk profiles within families. Results: A significant hazard ratio (HR) of 4.9 (95% CI: 1.9 - 13.9, p=0.003), confirmed a higher probability of developing schizophrenia for relatives of C9orf72 carriers compared to non-carriers. In total eight relatives of C9orf72 carriers experienced an episode of late-onset psychosis unrelated to schizophrenia, in comparison to one non-carrier (HR=17.9, 95% CI: 2.2, 143.2, p=0.007). The probability of suicide was also significantly higher for family members of C9orf72 carriers (HR=2.7, 95% CI 1.2,6.2, p=0.02). A HR of 2.7 (95% CI: 1.1 - 6.9, p=0.03) indicated a higher probability for Autism Spectrum Disorder (ASD) in family members of C9orf72 carriers, and this risk extended to FTD. Furthermore, there was a positive association between psychosis in probands and mental health disorders including ASD in their family members (p=0.04). Conclusion: Overall the results from this study suggest that a psychiatric phenotype exists within C9orf72 kindreds, Further studies should attempt to delineate the risk for psychiatric disorders in C9orf72 kindreds, to aid in clinical decision-making particularly regarding genetic counseling, through collaborations between neurology and psychiatry.