Evidence for Transgenerational Effects on Autism Spectrum Disorder Using Multigenerational Space-time Cluster Detection

Abstract

BACKGROUND AND AIM: Space-time cluster analyses are commonly used in spatial epidemiology. There is evidence of transgenerational factors associated with ASD. Space-time clusters of parents and grandparents of ASD cases may provide evidence of transgenerational effects and generate hypotheses regarding ancestral conditions associated with ASD. The Aim of this study is to identify and describe space-time clusters of ancestors of individuals with a clinical diagnosis of ASD. METHODS: Parents and grandparents of diagnosed ASD individuals were identified using the Utah Registry of Autism Developmental Disabilities (URADD) linked to their pedigrees in the Utah Population Database (UPDB). Inclusion criteria for ASD case ancestors included (1) three generations of continuous Utah residency, and (2) first reported case of ASD in the family. Ancestors of individuals without ASD were selected based on a 2:1 random sample matched by age, time-period, and sex to the ASD cases. Residential addresses of the ancestors for their perinatal, childhood and adolescent time periods were compiled from administrative databases linked to the UPDB and geocoded. Bernoulli space-time scan statistic was used to identify clusters for each type of ancestor and developmental window. RESULTS:The study included 7,914 parents and 15,828 grandparents generated from 3,957 ASD cases. Over 90% of the addresses were geocoded to street address. Twenty statistically significant space-time clusters (p-value 0.05) were identified (13 increased relative risk (RR) and 7 with RR1). The four strongest clusters (RR = 2.74 – 2.96) were from paternal grandparents at the perinatal time-period spanning 1 to 10 years and covering 8 to 132 km2 in predominantly urban residential areas. Of the 13 clusters with RR1 (range=1.27 – 2.96) 11 began between 1946 and 1960, nine were grandparents. CONCLUSIONS:Multiple very high relative risk space-time clusters of ASD ancestors during early life provide evidence of potential transgenerational effects on ASD in grandchildren. KEYWORDS: Space-time clustering, Multigenerational, Autism Spectrum Disorder, Transgenerational Effects