1 1 association between asmt and autistic-like traits in children 2 from a swedish nationwide cohort 3

1 Persons with autism spectrum disorders (ASDs) often display low levels of melatonin, and it 2 has been suggested that this decrease may be due to low activity of the acetylserotonin O3 methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, 4 genetic variants in ASMT have been associated with autism, as well as with low ASMT 5 activity and melatonin levels, suggesting that the low ASMT activity observed in autism may 6 partly be due to variation within the ASMT gene. In this study, we present a symptom-based 7 approach to investigate possible associations between ASMT and autistic-like traits (ALTs) in 8 the general population. To this end, continuous measures of ALTs were assessed in a 9 nationally representative twin cohort (n=1771) from Sweden and six Single Nucleotide 10 Polymorphisms (SNP) and a duplication of exon 2 to 8 in ASMT were genotyped. Our results 11 show a nominally significant association, in girls, between one SNP (rs5949028) in the last 12 intron of ASMT and social interaction impairments. No significant association, however, was 13 observed with traits related to language impairment or restricted and repetitive behavior. In 14 conclusion, our results support the possible involvement of the ASMT gene in ASDs and our 15 finding that only one of three traits shows association suggests that genetic research may 16 benefit from taking a symptom-specific approach to identify genes involved in autism 17 psychopathology. 18 19